bluuebunny/crossref_metadata_2025 huggingface dataset:
Preventive screening of open‐angle glaucoma: an innovative machine learning risk assessment tool based on health insurance claims data
Authors: Bremond‐Gignac Dominique , Dairazalia Sanchez‐Cortes , Jihyun Lee‐Engler , Maxime Coriou , Duru Gerard , Nicolas Loeillot , Ariel Beresniak
Published: January 2022

Purpose

Despite progress in management of open‐angle glaucoma, early diagnosis remains difficult due to delayed ophthalmologist consultation. Early glaucoma treatment avoids vision loss, thus developing automated detection methods is of importance for public health. We used supervised machine learning models on medical insurance claims data to identify at‐risk patient profiles that would benefit from undergoing glaucoma diagnosis, leading to early detection.

Methods

Using medical claims records from a Swiss health insurance company, we identified a “glaucoma group” composed by 2700 patients (18–65 yo) with at least 3 years of historical data in the database and at least one year of medications for lowering intraocular pressure. To complete the training dataset, we randomly selected a “non‐glaucoma control group” (N = 2700) with same age range and medical criteria. Random Forest models were then trained using patient medical consumption data (e.g. number of drugs, number of consultations, ocular tests) in order to estimate individual’s probability of having glaucoma based on medical claims records. Population was split into training set (70%) and test set (30%) to estimate the model prediction performance.

Results

The mean age of population with glaucoma was 55.3 (SD: 11.3), and had an average of 1.96 (SD: 2.8) eye visits within the 3 years period prior to their first glaucoma prescription. t‐test showed significant association between consumption of eye products (e.g. artificial tears) during the two years prior to glaucoma medication. The Random Forest classifier accuracy computed on the test set (N = 1600) showed a positive predictive value of 78.5%, a negative predictive value of 79.2%. Sensitivity and specificity were of 79.4% and 77.2% respectively.

Conclusions

To our knowledge, this study is the first to attempt estimating glaucoma probabilities from medical consumption invoice data. Our preliminary results show that using supervised machine learning algorithms could identify high‐risk patient profiles of glaucoma with an accuracy of almost 80%. These patients may benefit from an early ocular examination. Automated screening based on medical claims data could thus allow improving open‐angle glaucoma‐related health outcomes, minimizing serious vision loss, and reducing health costs.
Multivariate normative comparison, a novel method for improved use of the retinal nerve fiber layer thickness to detect early glaucoma
Authors: Chua Jacqueline , Schwarzhans Florian , Wong Damon , Li Chi , Vass Clemens , Schmetterer Leopold
Published: January 2022

Purpose

To assess whether compensating the RNFL thickness for multiple demographic and anatomical factors improves the detection of glaucoma.

Methods

This case‐control study enrolled 2699 healthy participants to construct and test a multivariate compensation model, which was then applied in 387 healthy controls and 387 glaucoma cases (early, n = 219; moderate, n = 97; and, advanced, n = 71). Participants underwent Cirrus spectral‐domain OCT (Carl Zeiss Meditec) imaging of the optic disc and macular cubes. Compensated RNFL thickness was generated based on ethnicity, age, refractive error, optic disc (ratio, orientation, and area), fovea (distance and angle), and retinal vessel density. RNFL thickness measurements and their corresponding areas under the receiver operating characteristic curves (AUCs) were obtained.

Results

After applying the Asian‐specific compensation model, the standard deviation (SD) of RNFL thickness reduced, where the effect was greatest for Chinese (16.9%), followed by Malays (13.9%) and then Indians (12.1%). Multivariate normative comparison outperformed measured RNFL for discrimination of early glaucoma (AUC = 0.90 vs 0.85; p < 0.001), moderate glaucoma (AUC = 0.94 vs 0.91; p < 0.001) and advanced glaucoma (AUC = 0.98 vs 0.96; p < 0.001).

Conclusions

The multivariate normative database of RNFL showed better glaucoma discrimination capability than measured RNFL thickness, which suggests there may be utility in accounting for demographic and anatomical variance in RNFL thickness to improve glaucoma detection.
Analysis of vitreous opacities in chronic glaucoma by vitreo‐optical coherence tomography imaging
Authors: Perié Manuel Subías , Campo Lorena Arias , Vicente Altabás María José , Fernández Álvaro Tello , Castro‐Roger Luisa , Palomar Elisa Viladés , Ciordia Beatriz Cordón , del Palomar Amaya Pérez , Cegoñino José , Montolio Alberto , Garcia‐Martin Elena , Rodrigo Maria Jesus
Published: January 2022

Purpose

To analyze the vitreous opacities of rat eyes by optical coherence tomography (OCT) in two models of chronic glaucoma. Hyperreflective opacities at the vitreoretinal interface, their dynamics over time (changes in number, size, intensity, eccentricity, and orientation) and as a function of intraocular pressure were analyzed in two different glaucoma models and compared to healthy controls.

Methods

Images of the vitreoretinal interface were obtained by OCT and exported as videos (composed of cross‐sectional images acquired by means of 61 b‐scans measuring around 3 mm in length and centred on the optic nerve). These videos were analysed using a custom program implemented in Matlab. The vitreous opacities, closely related to the immune cells, were analysed.

Results

Hyperreflective opacities, extrapolated as soma areas, were classified according to their size: isolated cells (<10 μm2), non‐activated cells (10–50 μm2), activated cells (50–250 μm2) and cell complexes (>250 μm2). In glaucoma models, right eyes showed significant increase of total area compared with left non‐induced eyes, and left eyes showed significant increase compared to healthy controls. The physiological number of opacities was 10–20. Glaucoma‐induced right eyes showed a mean of 70 opacities, a specular response between activated cells and non‐activated cells, and a greater variation in intensity in the smallest cells, that showed an early change in orientation compared with physiological eyes.

Conclusions

Our method of analyzing vitreous opacities by OCT could serve as a reliable neuroimaging biomarker to detect disease onset and early progression applicable to glaucoma and potentially other neurodegenerative diseases impacting the retina and optic nerve.
Posture‐dependent collapse of the optic nerve subarachnoid space: a combined MRI and modeling study
Authors: Holmlund Petter , Støverud Karen , Wåhlin Anders , Wiklund Urban , Malm Jan , Jóhannesson Gauti , Eklund Anders
Published: January 2022

Purpose

Large trans‐lamina cribrosa pressure differences (TLCPD) have been suggested to play a role in the development of normal‐tension glaucoma. To avoid substantial increases in the TLCPD in upright postures, we hypothesize that a collapse of the optic nerve subarachnoid space (ONSAS) protects the eyes from large TLCPDs when we stand up, i.e., by preventing low cerebrospinal fluid pressures around the optic nerve. In this study, we combined magnetic resonance imaging (MRI) and mathematical modeling to investigate the suggested ONSAS collapse and its effects on the TLCPD.

Methods

First, MRI was performed on six healthy volunteers in 6° head‐down tilt (HDT) and 13° head‐up tilt (HUT) to assess changes in ONSAS volume with changes in posture. The volume change represents optic nerve sheath distensibility. Second, we used the MRI data and mathematical modeling to simulate the ONSAS pressure and the potential ONSAS collapse in a fully upright posture (90°).

Results

The MRI showed a decrease of 33% in the ONSAS volume when going from the HDT to the HUT position (p < 0.001). In the upright posture, the simulations predicted an ONSAS collapse in the orbital section of the optic nerve, disrupting the pressure communication between the ONSAS and the intracranial subarachnoid space. The collapse reduced the simulated postural increase in TLCPD by roughly 1 mmHg, although this reduction was highly sensitive to the optic nerve sheath distensibility, varying between 0–4.8 mmHg when varying the distensibility by ±1 SD.

Conclusions

The ONSAS volume along the optic nerve is posture dependent during acute posture changes. The simulations supported the hypothesized ONSAS collapse in the upright posture and showed that even small changes in optic nerve sheath stiffness/distensibility may substantially affect the TLCPD, and thereby bear relevance for suggested TLCPD‐related disorders such as normal‐tension glaucoma.

Ref‐erence

Holmlund, P. et al. Posture‐Dependent Collapse of the Optic Nerve Subarachnoid Space: A Combined MRI and Modeling Study. IOVS 62.4 (2021).
The ubiquitin‐proteasomal pathway in glaucomatous lamina cribrosa cells
Authors: McElhinney Kealan , Irnaten Mustapha , Wallace Deborah , O'Brien Colm
Published: January 2022

Purpose

Primary open‐angle glaucoma (POAG) is an age‐related fibrotic condition and a leading cause of blindness worldwide. POAG‐related damage is initiated within the lamina cribrosa (LC) region of the optic nerve head, driven by the pathological activation of resident LC cells. LC cells bear striking similarities to proliferative, apoptotic‐resistant myofibroblasts known to be responsible for organ fibrosis. Myofibroblast dysregulation is linked to targeted proteasomal degradation of p53 by the E3 ubiquitin‐protein ligase MDM2 (mouse‐double‐minute‐2) thus negating p53’s important regulatory role in cell‐cycle/apoptosis. This project aims to evaluate the role of p53, MDM2, and the ubiquitin‐proteasomal pathway in glaucomatous LC cells.

Methods

Primary human normal LC (NLC) and glaucoma LC (GLC) cells (n = 3 donors) were cultured under standard conditions and treated for 48 hours with RG‐7112 (p53‐MDM2 interaction inhibitor, Abcam). The p53‐MDM2 ubiquitin‐proteasomal pathway was analysed by real‐time polymerase chain reaction (qRT‐PCR) for gene expression and protein levels via western blotting.

Results

MDM2 gene expression levels were significantly elevated (p = 0.006) in GLC cells (1.00 ± 0.12) versus NLC cells (0.89 ± 0.08). p53‐MDM2 inhibitor RG‐7112 treatment caused a further significant (p = 0.001) increase in MDM2 transcription levels in GLC cells (1.17 ± 0.04). p53 transcription levels were equivocal between GLC cells (0.88 ± 0.09) and NLC cells (0.87 ± 0.08), with RG‐7112 treatment leading to a significant increase (p = 0.028) in p53 transcription levels in GLC cells (0.95 ± 0.06). Western blot analysis showed significant decreased protein expression levels of p53 (0.76 ± 0.09)(p = 0.047) and increased protein expression of MDM2 (1.57 ± 0.33)(p = 0.042) in GLC cells compared to NLC. Interestingly, p53‐MDM2 inhibitor RG‐7112 treatment increased p53 (1.14 ± 0.43)(p = 0.267) and decreased MDM2 protein expression levels (0.92 ± 0.25)(p = 0.06) in GLC cells.

Conclusions

Our data suggest the ubiquitin‐proteasomal pathway is significantly dysregulated in GLC cells with MDM2 led p53 protein degradation negatively impacting its key role as “guardian of the genome”. Targeting the p53 ubiquitin‐proteasomal pathway in lamina cribrosa fibrosis may lead to future novel therapeutic interventions.
Resveratrol nanoparticles reduce retinal ganglion cell loss in glaucoma
Authors: Shamsher Ehtesham , Guo Li , Davis Benjamin M. , Luong Vy , Ravindran Nivedita , Somavarapu Satyanarayana , Cordeiro M. Francesca
Published: January 2022

Purpose

Resveratrol is a natural polyphenol found in red wine and dark chocolate known for its antioxidant, anti‐inflammatory and anti‐apoptotic properties. All these properties can be used to treat neurodegenerative diseases such as glaucoma. To date, resveratrol low solubility in water and bioavailability limits its clinical use. The goal of this study was to develop a novel nanoparticle formulation of resveratrol and to assess it in an ocular hypertension (OHT) rat model of glaucoma.

Methods

Resveratrol nanoparticles (RNs) were formulated using a thin film rehydration technique. OHT rat model was induced with the injection of 1.85 M normal saline solution in two episcleral veins of the left eye of 10 Dark Agouti rats. The right eye was used as an internal control. RNs (n = 5) or vehicle (n = 5) were given topically as an eye drop daily for 3 weeks from induction. After 3 weeks, rats were imaged with the Detection of Apoptosing Retinal Cell (DARC) technology. DARC count was defined as the number of apoptosing retinal cells counted by a masked investigator. Next, all rats were sacrificed, and their retinas immunostained with Brn3a antibody. Retinal Ganglion Cell (RGC) density ratio was defined as the ratio between the left treated and the right untreated eye (control).

Results

RNs were formulated with an encapsulation efficiency >70% and a stability >90 days. They were well‐tolerated without any sign of ocular irritation and neuroprotective in the OHT glaucoma model as evidenced by the reduction of RGC apoptosis compared to the vehicle (1.02 ± 0.05 vs 0.70 ± 0.11 RGC density ratio, p < 0.05). RNs did not reduce the Intraocular Pressure (IOP) suggesting that their effect was independent from IOP modulation. However, RNs were not able to reduce significantly DARC count compared to the vehicle (493 ± 83 vs 612 ± 84 DARC count, p > 0.05).

Conclusions

These promising results show that topical administration of RNs is neuroprotective in an OHT glaucoma rat model by reducing significantly RGC apoptosis. DARC count reduction is not significant owing to the low number of animals used. Therefore, bigger studies are needed to confirm these encouraging results.
Scleral fixation of intraocular lenses using MERSILENE suture
Authors: Fehmy Nafaa , Meriem Ouederni , Ahmed Selmi , Maamouri Rym , Elyes Jerbi , Monia Cheour
Published: January 2022

Purpose

To report the outcomes of the scleral fixation of intraocular lens using MERSILENE suture technique in the absence of adequate capsular bag support

Methods

We report a retrospective study carried out in the ophthalmology department of Habib Thameur hospital (Tunis, Tunisia) of patients who underwent scleral fixation of Bausch and Lomb Akreos AO60 IOL using MERSILENE suture 5‐0. All patients were evaluated for surgical indication, complete ocular examination pre and postoperatively was performed including refractive status, intraocular pressure (IOP) as well as anterior segment evaluation and fundus examination

Results

We included 12 eyes of 10 patients operated using the mentioned surgical technique. Surgical indication was Ectopia Lentis for 5 eyes, post‐traumatic lens dislocation for 3 eyes, post‐traumatic IOL dislocation for two eyes and surgical management of postoperative aphakia in two eyes. Best corrected visual acuity increased from 1.15 logMAR preoperatively to 0.49 logMAR at 6‐months postoperatively, with an average gain of 0.66 logMAR. Mean postoperative IOP was 15.5 mmHg. Complications included post‐operative hypotony in 3 eyes resolved with medical treatment, conjunctival inflammation and erosion due to an unburied knot after one month in 2 eyes managed with topical antibiotic and steroids followed by surgical burial of the knot.

Conclusions

Scleral fixation of Akreos AO60 IOL with MERSILENE suture is a safe, economical and well tolerated procedure leading to improvement of visual acuity. MERSIENE suture use appears to be effective and safe without suture‐related complication on the short‐term. However, long‐term assessment and comparative studies will be necessary to extend our results.
Spontaneous lens subluxation into anterior chamber. Importance of an early management
Authors: El Bakkali Ismael Bakkali , Arias Pablo Cisneros , El Bakkali Mohamed Bakkali , Rivasés Guillermo Pérez , de Rivas Marta Orejudo , Murillo Ana Boned , Núñez Moscarda Eva Josefina , Díaz Barreda María Dolores , Buey Sayas María Ángeles Del , Ascaso Puyuelo Francisco Javier
Published: January 2022

Purpose

To describe the importance of applying an urgent protocol in cases of lens subluxation into the anterior chamber (AC) in order to diminish the risk of corneal decompensation.

Methods

A 60‐year‐old man with a history of ocular trauma in his youth and pseudoexfoliation syndrome, presented pupillary block in the right eye 2 months after an accidental fall without ocular involvement. Visual acuity was 0.05 (decimal) and intraocular pressure was 55 mmHg. Slit lamp examination and anterior segment Optical Coherence Tomography showed a lens subluxation towards AC (lower portion) with endothelial contact and corneal edema. In funduscopy, an inferior giant tear with associated retinal detachment was observed.

Results

After treating ocular hypertension with hypotensive agents, Pars Plana Vitrectomy 25 Gauge + Lensectomy + Endolaser + SF6 Tamponading gas were performed, leaving the patient in aphakia for subsequent intraocular lens implantation surgery. Two months later, a substantial loss of endothelial cell count was observed (777 cells right eye VS 2223 cells left eye).

Conclusions

In this type of pathology, it is imperative to take immediate pharmacological, postural and surgical measures to reduce contact between the lens and the cornea, in order to minimize endothelial damage and improve the visual prognosis of these patients.

Bibliography

Ke G, Zhou E, Zhu K, Wei Y, Wang Z, Jia Y, Wang S, Gu Y. Retinal break associated with traumatic lens dislocation or subluxation requiring vitrectomy. Graefes Arch Clin Exp Ophthalmol. 2020 Mar;258(3):693–697. doi: 10.1007/s00417‐019‐04530‐9. Epub 2019 Nov 28. PMID: 31781882.

Salehi‐Had H, Turalba A. Management of traumatic crystalline lens subluxation and dislocation. Int Ophthalmol Clin. 2010 Winter;50(1):167–79. doi: 10.1097/IIO.0b013e3181c567de. PMID: 20057305.
Pharmacogenetics. Phenotype and genotype response to prostaglandin analogues and beta bloquers in a population of glaucoma patients
Authors: Toro Valeria Opazo , Milla Elena , Boquera Claudia , Llanas Berta , Brunet Mercè
Published: January 2022

Purpose

Research about phenotypic and genotypic characteristics from a sample of glaucoma patients, and the pharmacological response to beta blockers (BB) and prostaglandin analogues (PGA).

Methods

139 eyes from 72 patients affected with glaucoma under BB and PGA treatment, were included in a prospective study. Single nucleotide polymorphism (SNP), were analyzed using real‐time PCR assays: prostaglandin F2α receptor (PTGFR) rs3766355 and 3753380; cytochrome‐p450‐2D6 (CYP2D6) rs16947 and 769258; beta 2 adrenergic receptor (ADBR 2) rs1042714. The other variables of the study were mean deviation (MD) of visual field, glaucoma surgery background, medication side effects, medical treatment, baseline and treated intraocular pressure (IOP).

Results

From a total of 139 eyes, 68 (48.9%) were right eyes. The main diagnosis was primary open angle glaucoma (66.2%). Additionally, 57(41%) eyes had some kind of glaucoma surgery and also 57(41%) eyes were under 3 or more medications (PGA+BB+other). Side effects were reported in 12 eyes (8.9%). IOP for baseline and treated patients were 26.55 ± 8.19 and 21.01 ± 5.54. The only significant differences were found among patient treated IOP in rs3766355 heterozygous(HT) 21.07 ± 0.607 mutated homozygous(HZ) 20.98 ± 0.639 and wildtype HZ 16 ± 1.08 (p = 0.031).The MD mean was −7.59 ± 8.63. Comparing the mean of MD in rs3766355 wildtype HZ −2 ± 2.2, HT −3.87 ± 4, mutated HZ −9.37 ± 9.51, significant differences were elucidated (p = 0.009). Likewise between MD and rs3753380 wildtype HZ −6.1 ± 8.67, HT −9.02 ± 8.63, and mutated HZ −9.51 ± 7.44 (p = 0.017).

Conclusions

Significant differences were found when comparing the MD in wildtype HZ, HT and mutated HZ carrying rs3766355 and rs3753380 to greater number of mutated alleles, greater defect in the visual field (MD). Likewise significant differences were found in the treated IOP in HZ and HT patients carrying a mutated rs3766355 allele with regard to HZ wildtype patients. Therefore, poor response to treatment may be associated with being a carrier of this mutated allele.
Optic disc pit: clinical and swept source optical coherence tomography characteristics
Authors: Maamouri Rym , Fehmy Nafaa , Wijdene Nabi , Meriem Ouederni , Hela Sassi , monia cheour
Published: January 2022

Purpose

To study clinical and swept source optical coherence tomography (SS‐OCT) characteristics in eyes with optic disc pit (ODP).

Methods

A retrospective case series of 7 eyes of 6 patients with ODP. All patients underwent a detailed ophthalmic examination, fundus photography and SS‐OCT scan of the macula and the optic disc.

Results

Mean age of diagnosis of ODP was 23 years old. Two patients were males and four patients were females. ODP was bilateral in one patient. It was associated with other ocular abnormalities in one eye. Three patients complained from blurred vision and three patients were asymptomatic. Mean BCVA at presentation in eyes with ODP was +0.5 LogMar. ODP was identified in funds examination in four eyes. SS‐OCT identified abnormalities of the optic disc in all eyes and showed ODP maculopathy in six eyes.

Conclusions

ODP is a rare congenital anomaly of the optic disc that can be associated with maculopathy leading to progressive visual deterioration. SS‐OCT is a noninvasive tool for diagnoses of this disease specially when ODP is not obvious on fundoscopy, it allows the diagnosis of ODP maculopathy and may identify the mechanism of fluid passage from the optic disc pit to the macula.
Cerebral arteriovenous fistulas and orbital presentation. Diagnosis and treatment
Authors: Konstantinidou Eleni , Karydas George , Kavroulaki Dimitra
Published: January 2022

Purpose

To present three cases of cerebral arteriovenous fistula with first clinical presentation from the orbit.

Methods

Three women (50, 82 and 87 years old) experienced unilateral eyelid swelling with conjunctival chemosis, proptosis, diplopia, blurred vision and increased intraocular pressure. No known history of brain injury, peri‐ocular or sinus infection. They underwent blood tests for endocrine, autoimmune or infectious disease, Ear‐Nose‐Throat (ENT) assessment, orbital computed tomography (CT) and magnetic resonance imaging (MRI), magnetic resonance angiography (MRA) and digital subtraction angiography (DSA).

Results

Blood tests and ENT assessment were negative, MRA did not show any related pathology. Orbital CT and MRI, with contrast agent, showed dilatation of the corresponding superior ophthalmic vein in all three patients. Two of them underwent DSA showing cerebral arteriovenous fistula (dural AVF) involving the cavernous sinus with retrograde blood flow to the ophthalmic vein. They underwent neurosurgical embolization of the fistula.

Conclusions

Cerebral arteriovenous fistulas involving the cavernous sinus may have only clinical presentation from the orbit and only imaging finding the dilatation of the corresponding ophthalmic vein in CT or MRI scans. In a case of unilateral proptosis and dilated conjunctival vessels, we should take into consideration the diagnosis of cerebral arteriovenous fistula.
Features of peripapillary hyperreflective ovoid mass‐like structures (PHOMS) according to their etiology
Authors: Hela Sassi , Aoun Safa Ben , Meriem Ouederni , Elyes Jerbi , Monia Cheour
Published: January 2022

Purpose

To compare clinical and multimodal imaging findings in patients with PHOMS and correlate them with the etiology.

Methods

A prospective descriptive comparative study carried out at the Ophthalmology Department of Habib Thameur University Hospital of Tunis between March 1st 2020 and March 30th 2021. Inclusion criteria were presence of blurred optic disc margins. Patients with optic disc drusen were excluded. All patients underwent complete ophthalmic examination, 24.2 Humphrey visual field (VF), fluorescein angiography (FA) and Swept‐Source Optical Coherence Tomography (SS‐OCT). Comparative Mann Whitney and chi‐squared tests were performed.

Results

Sixteen eyes of 8 patients were eligible for the study. Mean age was 41.63 years +/‐ 10.49 years. Mean Best Corrected Visual Acuity was 0.23+‐0.27 log MAR. Main etiologies were sequelae of idiopathic intracranial hypertension (IIH) in 8 eyes (50%) and tilted disc syndrome (TDS) in 6 eyes (37.5%). VF defects were found in 12 eyes (75%). They included non‐specific scotomas (35.7%), blind spot enlargement (21.4%) and peripheral arcuate defect (12.5%). Peripapillary Retinal Nerve Fiber Layer (pRNFL) were thickened in 62.5% of eyes, altered in 31.3% and preserved in 6.3%. Inferior and nasal pRNFL showed no alterations in all eyes. SS‐OCT revealed hyperreflective lesions in all eyes, associated to posterior shadowing in 12 eyes (75%), hyperreflective dots in 10 eyes (62.5%) and peripapillary pigment epithelium detachment in 9 eyes (56.3%). There were no statistically significant differences in VF alterations between TDS and IIH group. Patients with IIH presented thicker pRNFL (p = 0.023) and were more likely to present annular leakage in FA (p = 0.012).

Conclusions

PHOMS is a recently described entity that can be related to several etiologies such as IIH, TDS or ischemic optic nerve neuropathy. Both TDS and IIH can lead to visual field defects. IIH is more likely to give annular retention in FA and thickening of pRNFL.
Congenital aniridia and strabismus
Authors: Sordello Lucie , Belilita Ines , Bremond‐Gignac Dominique
Published: January 2022

Purpose

Congenital aniridia is a panocular disease with congenital absence of iris. Congenital Aniridia affects, beyond iris, cornea, angle structures, lens and fovea, and possibly associated with other anomalies. This genetic rare disease can cause severe visual impairment occurring from various mechanisms as glaucoma, limbal insufficiency and foveal hypoplasia. PAX6 gene is mainly involved in the disease. We aim to understand the features of patients with congenital aniridia and strabismus from 1 yo to 30 yo, identifying the characteristics of oculomotor anomalies.

Methods

We analyse our 330 aniridia patients cohort in a retrospective study to identify patient with a good fixation and minimal cooperation. All patients underwent history of the disease, a complete ocular examination with ophthalmic exploration, orthoptic and had genetic molecular analysis.

Results

Of the 330 subjects cohort, 36 patients, 23 females and 13 males (range 1 yo to 30 yo) were identified and diagnosed with strabismus with mean age of 11.02 yo. A family history was reported in 55% of the patients. Marked nystagmus was present in 69% of the cases. Foveal hypoplasia from Thomas classification, was observed in all patients and Grade IV in 86% of cases. Esotropia was observed in 38.8%, exotropia in 36.1% and hypertropia in 5.5%. Associated congenital cataract is described and worsened the strabismus.

Conclusions

Our study demonstrated a high frequency of strabismus in congenital aniridia. Marked nystagmus and associated congenital cataract worsened the strabismus treatment. In this rare disease, further studies are required for the follow‐up of aniridia patients in order to get better therapeutic options.
The use of computer‐aided design/computer‐aided manufacturing technologies in the treatment of endocrine orbitopathy: pro and contra
Authors: Prusak Olha
Published: January 2022

Purpose

To study the advantages and disadvantages of using CAD/CAM technologies in the treatment of endocrine orbitopathy.

Methods

Research analysis of modern scientific publications, Sim Plant 13.02 software environment and Geomagic Freeform Plus.

Results

According to the literature, the frequency of complications of surgical decompression of the orbit is from 9.3% to 35% (most often ‐ the appearance of secondary diplopia, less often ‐ lesions of the hyoid nerve, cerebrospinal fluid leakage, epistaxis, bleeding in the orbit, etc. [Leong, 2009, Sellari‐Franceschini, 2016]. As patients today expect excellent functional and aesthetic results of surgical treatment, the urgent problem is to find new opportunities for planning and performing surgical decompression of the orbit, including the use of Computer‐Aided Design (CAD)/Computer‐Aided Manufacturing (CAM) technologies. Given the need for an individualized approach to the patient, the use of CAD/CAM technology in the treatment of endocrine orbitopathy has a number of advantages: obtaining three‐dimensional models of the skull expands the study of anatomy of the orbital walls, its volume, exophthalmos and minimization of intraoperative complications. The disadvantages of using CAD/CAM technologies are the multi‐stage and time‐consuming process (multislice computed tomography and data export to the software environment, segmentation of anatomical objects and creation of virtual three‐dimensional models, printing of resection surgical templates by stereolithography) and high cost.

Conclusions

The use of CAD/CAM technologies to optimize surgical decompression of the orbit in patients with endocrine orbitopathy has a number of advantages and disadvantages.
Investigating the effects of docetaxel on rat eye
Authors: Unsal Ayse Ipek Akyuz , Kahyaoglu Fadime , Onal Tuna , Demir Bilgin , Barutca Sabri , Demirci Buket
Published: January 2022

Purpose

Docetaxel (DTX) is a widely used chemotherapeutic agent in breast, prostate and lung cancers. Approximetly 60% of patients face ocular disorders including epiphora, stye, blepharedema, dacryostenosis, corneal and conjunctival disorders, entropion and blurred vision. The aim of this study is to investigate the effects of DTX on rat eye

Methods

This study mainly planned to assess the alopecia effect of DTX, but the remained eye tissues have been evaluated to decrease the animal number used in medical researches. 6‐8 months old albino male Wistar rats (n = 7) were given 10 mg/kg intraperitoneally (i.p) DTX treatment three times at the 0th, 8th, 15th days. Control group (n = 6) was administered serum physiologic i.p once a week. The ocular tissues are taken at the 22nd day and evaluated by Hematoxylin&Eosin staining. TGF‐beta and TNF‐alfa stains were planned.

Results

Preliminary results of this study revealed conjunctival epithelial degeneration, corneal neovascularization, mild‐severe retinal nerve fibre layer degeneration, inflammation and cystic dilatation of lacrimal gland, increased capillary vessel density and vacuolar degeneration of optic nerve. The findings were demonstrated in Fig 1,2 and 3.

Conclusions

DTX cause serious ocular disorders and this is the first experimental study investigating these effects histologically. Increasing number of cancer cases and frequent use of Docetaxel, urges ophthalmologist to be aware of its ocular side effects.
3D MRI tumour measurements for treatment planning of eye tumours
Authors: Klaassen Lisa , Jaarsma‐Coes M.G. , Ferreira T.A. , Vu T.H.K. , Marinkovic M. , Luyten G.P.M. , Rasch C.R.N. , Beenakker J.W.M.
Published: January 2022

Purpose

We aim to evaluate 3D definitions of prominence for uveal melanoma (UM), and compare US and contrast‐enhanced T1‐weighted MRI measurements for the most appropriate definitions.

Methods

25 UM patients were scanned at 3 Tesla MRI with a 4.7 cm surface coil [1]. The tumour was delineated on the 3D contrast‐enhanced T1‐weighted images (voxel size 0.8 x 0.8 x 0.8 mm3). Three prominence definitions were evaluated. Promhaus: the distance to the tumour point most distal from sclera. Promsclera: similar to promhaus, but distances are measured perpendicular to the sclera. Promcentre: distance between most interior part of the tumour and sclera. The most appropriate definition was chosen and compared to the clinical ultrasound measurements. Differences >0.5 mm were considered significant.

Results

For 13/25 patients, there was no significant difference between three definitions. For 12 patients, promsclera or promhaus yielded an oblique measurement or a measurement at the tumour edge. As these measurements are unsuitable for radiotherapy dose calculations, promcentre was selected as the most appropriate definition. For 7 patients, the difference between the US prominence and promcentre was >0.5mm (median absolute difference 0.3 mm, range 0.0–1.6 mm). In 3/7 patients, the MRI measurement was considered more accurate than the US measurement, as the tumour top was not visualized on US.

Conclusions

After evaluation of 3D prominence definitions for MRI, the median absolute prominence difference (0.3 mm) was below the MRI voxel size and the inter‐observer variability for US measurements [2]. Largest differences were observed in patients where US tumour visualization was incomplete, in which case MRI was preferred. For prominence differences in patients with tumours adjacent to the optic nerve or with enhancing sclera, further study is needed to determine the most accurate method.

Bibliography:

1. Ferreira et al. Cancers (2019)

2. Haritoglu et al. Br J Opth (2002)
Orbital presentation of Langerhans cell histiocytosis
Authors: Díaz Oier Pérez , Reina Alfonso Rubio , de Paz Sergio Pérez , Cardeñosa Nuria Cuenca , López Fernando Sellers
Published: January 2022

Purpose

To analyze and review an ophthalmic manifestation of an uncommon pathology such as Langerhans cell histiocytosis (LCH).

Methods

Single‐patient case report.

Results

LCH is an uncommon disorder produced by mononuclear phagocyte system cell proliferation, resulting in antigen‐presenting cells similar to Langerhans cells invading bone, skin, bone marrow, lymphatic nodes, liver, spleen and central nervous system (CNS). The number and location of affected organs is key in treatment and prognosis. In this case report, a 16‐year‐old girl presented 10 day‐long superoexternal orbital pain associated with palpebral edema, making acute dacryoadenitis and preseptal cellulitis the most common differential diagnoses. After poor response to antibiotic and anti‐inflamatory oral treatment, CT scan was ordered, showing an osteolytic frontal mass at the superoexternal orbital roof, expanding to extraconal space and anterior cranial fossa. With a differential diagnosis of LCH, osteomyelitis, hematologic disease or vascular malformation, among others, a biopsy was performed, confirming the LCH diagnosis. An extension exam was performed, excluding new tumors, reaching a diagnosis of a monostotic bone form of LCH. Chemotherapy with prednisone and visblastine was advised due CNS affectation risk because of the tumor’s location, with evident but incomplete response after six‐week induction and complete response after a second six‐week induction cycle. The patient is currently ongoing consolidation chemotherapy.

Conclusions

Orbital tumors are not frequent in pediatric ages, but they must be included in the differential diagnosis of orbital cellulitis, since that can be the first manifestation of these tumors.
Class2, 1p loss, 8q gain uveal melanoma: a case report
Authors: Demková Lucia , Šoltýsová Andrea , Kajabová Viera Horváthová , Danková Zuzana , Jašek Karin , Dvorská Dana , Babál Pavel , Furdova Alena , Smolkova Bozena
Published: January 2022

Purpose

Metastatic spread of uveal melanoma (UM) is associated with epithelial‐mesenchymal transition (EMT). This process is not sufficiently investigated in UM due to its neuroectodermal origin. Herein we present a case study of 1p loss, 8q gain in a locally advanced UM patient enrolled after the onset of metastatic disease.

Methods

UM‐specific chromosomal rearrangements were assessed by MLPA, transcriptomic analysis using the Agilent microarray platform. Vital tumor cells were injected subcutaneously into NSG® mice to develop patient‐derived xenografts (PDX). Nine hot‐spot mutations in four genes (GNA11, GNAQ, PLCβ4, and CYSLTR2) were investigated by digital droplet PCR (ddPCR).

Results

The tumor and the heterogeneous tumor‐bearing mass in the right orbit were confirmed as a malignant neoplasm with an unfavorable immunophenotype, poor prognosis Class 2 gene expression profile, 1p loss, and 8q gain. GNA11 p.Q209L mutation with high plasmatic ctDNA copy numbers (n = 108/ul) was found by ddPCR. Despite the lack of monosomy 3, PDXs were successfully derived, with high vimentin expression in the second passage.

Conclusions

1p loss and 8q gain were associated with the distinct gene expression pattern of EMT‐associated genes, unfavorable phenotype, and development of PDX.

This work was supported by APVV‐17‐0369 and VEGA 1/0395/21 grants.
Monitoring proliferative diabetic retinopathy with optical coherence tomography angiography
Authors: Enders Christian , Jens Ulrich Werner
Published: January 2022

Purpose

To assess the longitudinal changes of neovascularisations (NV) in a patient with proliferative diabetic retinopathy (PDR) after panretinal photocoagulation under additive intravitreal treatment with Vascular Endothelial Growth Factor (VEGF)‐inhibitors using optical coherence tomography angiography (OCTA).

Methods

We present two patients after several sessions of panretinal photocoagulation and intravitreal treatment with VEGF‐Inhibitors due to DME and also to treat PDR. Multimodal imaging including fundus photography and optical coherence tomography angiography (OCTA) was used to monitor the effect of VEGF‐inhibitors on the NV. We measured the size of the NV at baseline and at 1, 3, and 6 months and also compared morphology of the NV.

Results

All neovascularisations of the disc and elsewhere showed a significant regression in morphology and also in their area. No adverse events were reported.

Conclusions

Successful treatment of PDR with VEGF‐Inhibitors with a significant regression of the NV could be shown by OCTA. In the future, treatment response should be closely monitored by using multimodal imaging including OCTA to guarantee the best therapy for our patients. Precise quantification of the neovascularization’s area by OCTA makes it a useful tool for monitoring the response of retinal neovascular lesions to anti‐VEGF treatment.
Quantitative optical coherence tomography angiography biomarkers for Alport syndrome
Authors: Maria Cunha Ana , Teixeira Daniela , Cabral Diogo , Estrela‐Silva Sérgio , Falcão‐Reis Fernando , Carneiro Ângela
Published: January 2022

Purpose

To evaluate microvascular abnormalities of patients with Alport syndrome AS using optical coherence tomography angiography (OCT‐A) quantitative biomarkers.

Methods

Cross‐sectional, prospective evaluation of consecutive patients with AS and healthy subjects. AS diagnosis was performed by genetic test. All participants underwent a retinal vasculature evaluation by spectral domain optical coherence tomography (SD‐OCT) and OCT‐A of the macula. Quantitative analysis included: whole vascular density (VD, %), foveal avascular zone area (FAZ, mm2), fractal dimension (FD) and lacunarity (LAC).

Results

Ninety‐four eyes were included in this study, 45 eyes from patients with AS and 49 eyes from healthy subjects. The pathogenic mutation in the COL4A5 gene on the chromosome X was found in 14 patients the pathogenic autosomal recessive mutations in the COL4A3 gene were found in 9 patients. Quantitative evaluation demonstrated a significant difference between AS and healthy subjects on LAC of the SCP and DCP (p < 0.001 and p < 0.001, respectively) and on FD in the DCP (p < 0.001).

Conclusion

The DCP Alport patients have a higher vessel nonuniformity than DCP of healthy subjects. We hypothesize that endothelial cells lesion in the setting of low resistance at the DCP circuit that could lead to long‐term structural disorganization.
Oral Ursodeoxycholic acid crosses the blood brain barrier in patients with retinal detachment and protects against retinal degeneration in an ex vivo model
Authors: Daruich‐Matet Alejandra , Jaworski Thara , Henry Hugues , Zola Marta , Youale Jenny , Parenti Léa , Naud Marie‐Christine , Delaunay Kimberley , Bertrand Mathilde , Berdugo Marianne , Kowalczuk Laura , Boatright Jeffrey , Picard Emilie , Behar‐Cohen francine
Published: January 2022

Purpose

The neuroprotective properties of hydrophilic bile acids are recognized but whether their oral administration can benefit to patients with retinal diseases is unknown. Rhegmatogenous retinal detachment (RD) is a threatening visual condition and a human disease model for retinal degenerations. Despite surgical reattachment, vision does not fully recover, due to subretinal fluid (SFR) and photoreceptor cell death, through mechanisms that recapitulate those of retinal degenerative diseases. We have measured the ocular concentration of Ursodeoxycholic acid (UDCA) administered orally to patients with RD. We then tested the effects and mechanisms of UDCA, at concentrations found in patient’s eyes, in RD models. Finally, we analyzed the neuroprotective effects of ocular fluids from treated patients.

Methods

26 patients with RD were included. 21 patients received UDCA before surgery. Ocular fluids samples were collected and bile acids were measured. Rat retinal explants and WERI‐Rb‐1 human cone cell line were exposed to albumin or patient’s SRF ± UDCA. Cell death markers and transcriptome were analyzed.

Results

UDCA was detected in ocular media after oral administration and its level correlated with protein concentration in SRF and extension of RD. At 6 months after surgery, visual recovery was superior in patients who had higher UDCA ocular levels.

UDCA levels measured in human ocular media, protected photoreceptors from apoptosis and necrosis in rats retinal explants exposed to albumin and UDCA protected WERI‐Rb‐1 cells from albumin‐induced death. Cell death was reduced in retinal explants exposed to SRF collected from UDCA‐treated patients as compared to SRF from controls. UDCA effects resulted from the up‐regulation of anti‐apoptotic, anti‐oxidant and anti‐inflammatory genes.

Conclusions

Oral UDCA reaches neuroprotective concentrations in patients with RD, showing its potential as an adjuvant to surgery but also in other retinal degenerative diseases.
Choroidal hyperreflective nodules detected by infrared reflectance images as a new diagnostic criterion for Neurofibromatosis ‐1
Authors: Orejudo deRivas Marta , Mateo Gabas Javier , Boned‐Murillo Ana , Díaz‐Barreda Mª Dolores , Cisneros Pablo , Núñez Moscarda Eva Josefina , El Bakkali Ismael Bakkali , Pérez Rivasés Guillermo
Published: January 2022

Purpose

To investigate the possibility of including the presence of choroidal abnormalities detected by infrared reflectance as a new diagnostic criterion for neurofibromatosis type 1 (NF1).

Methods

A cross‐sectional study was carried out in 24 eyes of 12 patients diagnosed with NF1 using the criteria of the National Institutes of Health (NIH). A group of 12 healthy individuals of equivalent age and sex served as control. The presence and number of visualized choroidal abnormalities were evaluated by Heidelberg optical coherence tomography (OCT) with infrared reflectance (NIR) as well as the presence of iridian Lisch nodules by slit lamp examination.

Results

NIR by OCT shows the presence of choroidal hyperreflective nodules in all the patients diagnosed with NF1, while these choroidal abnormalities are not observed in any control. This finding is more frequent than the presence of iridian Lisch nodules.

Conclusions

Hyperreflective nodules detected by NIR appear more frequently than Lisch nodules in NF1. The study suggests that it could be considered as a new diagnostic criterion for NF1.
Identification of eleven differentially expressed proteins in the tear film of patients with neovascular Age‐related Macular Degeneration (AMD)
Authors: Winiarczyk Mateusz , Winiarczyk Dagmara , Michalak Katarzyna , Kaarniranta Kai , Adaszek Łukasz , Winiarczyk Stanisław , Mackiewicz Jerzy
Published: January 2022

Purpose

The exact mechanisms underlying the age‐related macular degeneration (AMD) are still not totally understood, but processes like inflammation, chronic oxidative stress (OS), and autophagy impairment, are currently believed to have strong influence of the disease development. There are multiple studies concerning changes of the proteome in different tissues in the course of AMD. As they all need invasive procedures to obtain a sample, we sought for a non‐invasive approach. Tear film can be a potential candidte for proteomic information regarding AMD.

Methods

Tear film was collected on Schirmer strips, 2D‐electrophoresis was performed, and Delta2D software was used for the identification of the differentially expressed proteins from the gels. The spots were excised, and identified by MALDI‐TOF mass spectrometer.

Results

30 patients were examined, 15 for each group. We have found 469 proteins in the analyzed samples, 11 differentiating proteins fulfilled the criteria of being statistically significant. 3 proteins were up‐regulated (Retinal dehydrogenase 1; ATP‐dependent translocase ABCB1; and alpha‐Enolase), and 8 were down‐regulated (Annexin A1; Annexin A4; Glutathione S‐transferase P; Aldo‐ketoreductase family 1 member A1; Allograft inflammatory factor 1; Cytospin‐A or Elongation factor 2; Short stature homeobox protein 2 and uncharacterized protein C11orf98).

Conclusions

Tear film can be used as a non‐invasively obtained source of proteomic information about cellular processes ongoing in the course of AMD. The differentially expressed proteins are involved in the choroidal neovascularization, inflammation, oxidative stress and autophagy impairment.
Effect of protein homeostasis modulation in primary cone degeneration
Authors: Almansa García Ana Cristina , Cao Bowen , Sen Merve , Bolz Sylvia , Arango‐Gonzalez Blanca , Ueffing Marius
Published: January 2022

Purpose

Degenerative cone disorders are an important group of inherited retinal degenerations as they severely disable visual acuity and color vision, causing a major impact on the quality of life of affected patients. These disorders are commonly classified as cone dystrophies and achromatopsia. The cone photoreceptor function loss‐1 (cpfl1) mutant mouse is a model for primary cone degeneration and shares a similar phenotype to patients with complete achromatopsia. Cpfl1 mutation affects the cone‐specific PDE6 gene, leading to a cGMP accumulation, increased Ca+ influx, and cell death. Moreover, M‐, S‐opsin and cone‐specific transducin mislocalization to the cell body have been reported (Trifunovic et al., 2016). Previously, the inhibition of valosin‐containing protein (VCP, an ATPase involved in the (ERAD)) has proven to be protective in different models of autosomal dominant retinitis pigmentosa restoring protein trafficking (Arango‐Gonzalez et al., 2020; Sen et al., 2021). This study aims to assess whether VCP inhibition can also be protective against cone photoreceptor cell death in a cpfl1 retinal organotypic culture system.

Methods

Cpfl1 retinal explants were maintained in serum‐free conditions and treated with two VCP inhibitors, ML240 and NMS‐873, from PN14 until PN24 (peak of cone degeneration). Photoreceptor cell survival, cone morphology, and opsin expression were evaluated by TUNEL staining, cell row quantification, and immunostaining.

Results

VCP inhibition resulted in an increased number of cell rows in the ONL of the treated explants compared with the control groups. The treated retinas also showed an improved cone morphology and a significant restoration of cone density up to levels similar to those observed in the wild type.

Conclusions

Our results suggest that modulation of protein homeostasis through VCP inhibition is protective in primary cone degeneration.