bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a new digital visual acuity chart for best‐corrected visual acuity estimation
Authors: Yu Zhaohua , Söderberg Per
Published: January 2021

Purpose

To compare estimated best‐corrected visual acuity (BCVA) between the digital chart named AxAnIvIs and the ETDRS chart at different level of acuity, and to determine if there is difference of the test time between the two systems.

Methods

Patients at the eye clinic of Uppsala university hospital that met the inclusion criteria (age >55 years, BCVA [1.0; −0.1] and no ocular disease strongly considered to cause visual acuity change within one month) were asked to participate this study. The AxAnIvIs system uses a custom made algorithm for optotypes visualisation where optotypes decrease in size horizontally in one line. Altogether 16 subjects (8 male, 8 female) were included and distributed equally to four visual acuity classes ([1.0 0.8], [0.7 0.5], [0.4 0.2], [0.1 −0.1] logMAR). Each subject’s BCVA was measured and the test time was recorded with the two systems on two separate occasions.

Results

The mean BCVA difference between the AxAnIvIs system and the ETDRS chart at visual acuity class of [1.0 0.8], [0.7 0.5], [0.4 0.2], [0.1 −0.1] logMAR was estimated as a CI(95%), 0.02 ± 0.04, 0.02 ± 0.08, ‐0.01 ± 0.05, 0.03 ± 0.07 logMAR, respectively. ANOVA shows that there is no significant difference between the two systems and no significant difference between the two systems at the different visual acuity classes. The mean test time between the AxAnIvIs system and the ETDRS chart was estimated as a CI(95%), −37 ± 15 s.

Conclusions

The AxAnIvIs system can be used as a replacement of the ETDRS chart for general examination. The test time with the AxAnIvIs system is half minute shorter than that with the ETDRS chart.
Tolerance to light of patients suffering from infectious keratitis
Authors: Courrier Emilie , Lambert Victor , Renault Didier , Garcin Thibaud , Caroline Trone Marie , Herbepin Pascal , Moine Baptiste , Thuret Gilles , Gain Philippe
Published: January 2021

Purpose

With very photophobic patients, the advantages of red or near infrared (NIR) light to develop new ophthalmology imaging devices seem obvious: no or little glare, possibility of long signal integration, no phototoxicity, and lesser autofluorescence of ocular tissues. Nevertheless, in this range, the shortest possible wavelength facilitates signal detection.

Aim

To determine the maximal irradiance tolerated with 6 wavelengths: 2 red, 2 far red and 1 NIR lights in order to determine the shortest wavelength well tolerated by patients, in comparison with the standard cobalt blue light of ophthalmology slit lamp.

Methods

Study design: interventional, monocentric, single group assignment study on 30 eyes of 30 patients with infectious keratitis after informed consent. Thanks to a customized machine from our laboratory, the photophobic eye was exposed to the 6 lights with increasing intensity. The patients switched off the light when the discomfort was too elevated. The maximal cumulative irradiance possible at 482, 650, 675, 700, 750 and 800 nm were respectively 171, 689, 759, 862, 920 and 889 mW/cm2.

Results

The maximal cumulative irradiance tolerated increased significantly with wavelength (p < 0.001). However, the difference was not significant between each increment. Thus, red at 675 nm gave a significantly higher cumulative irradiance than blue at 482 nm. Red at 700 nm did not provide significant gain; however, far red at 750 nm still provided additional gain, but not at 800 nm. The shortest wavelengths were stopped more quickly and more than 50% of patients reached the maximum irradiance delivered by the source at 750 and 800 nm.

Conclusions

We demonstrate that a light source at 750 and 800 nm can be used for ophthalmic imaging with good tolerance in the photophobic patient.
Dural carotid cavernous sinus fistula: outcome after endovascular treatment or conservative management
Authors: José Patrícia , Teixeira Filipa , Raposo Francisco , Biscoito Luísa , Claúdia Fonseca Ana , Simões Silva Filipe
Published: January 2021

Purpose

To analyze the efficacy of endovascular treatment and conservative management in patients with dural arteriovenous sinus fistula.

Methods

Retrospective and observational study, including patients with dural carotid cavernous fistula followed at Ophthalmology and Neuroradiology departments of Hospital Santa Maria – Lisbon between 1991 and 2019. Patient demographics, risk factors, symptoms, etiology, angiographic findings and clinic outcome were studied.

Results

Nineteen patients were included. 53% were female and mean age at diagnosis was 64 years (range from 10 to 78). Atherosclerosis risk factors were identified: hypertension (79%), diabetes (21%) and hyperlipidemia (21%). Ocular symptoms were the only presentation of the disease, with proptosis and hyperemia being the main clinical signs. Bilateral fistula was found in 16%. Spontaneous fistula occurred in 81% and trauma history was identified in 19%. %. According to Barrow angiographic classification, 11% were grade B, 21% C and 58% D. Endovascular treatment by transvenous/transarterial embolization was performed in 79% (n = 15), 73% with complete exclusion in a mean of 8.6 ± 17.4 months. The mean follow‐up was 4.0 ± 3.1 years after procedures. Conservative management was performed in 21% (n = 4) and the last follow‐up was 3.5 ± 5.0 years. In both groups, most patients (65–75%) showed symptoms and ophthalmologic examination improvement. After endovascular treatment, visual acuity was maintained (0.7 ± 0.4), and there was intraocular pressure reduction (25.1 ± 6.5 to 15.0 ± 2.3 mmHg). In patients with conservative management, there was no change in visual acuity (0.4 ± 0.5) and intraocular pressure decreased with medication (29.3 ± 9.5 to 19.3 ± 9.2 mmHg). Secondary ocular hypertension (25%) was a long‐term complication of carotid cavernous sinus fistulas.

Conclusions

Ocular symptoms are the most frequent presentation of dural carotid cavernous fistula, with ocular hypertension as the commonest complication. In less symptomatic patients, the risks and benefits of endovascular treatment should be considered, as conservative treatment may be an option.
Ex vivo models of human ocular surface regeneration indicate that conjunctiva possess the capacity of restoring corneal epithelium
Authors: Perrache Chantal , Poinard Sylvain , Gain Philippe , Thuret Gilles , He Zhiguo
Published: January 2021

Purpose

We recently showed that corneas stored in the corneal bioreactor (BR) that restores IOP and storage medium renewal had increased endothelial viability and enzymatic pump expression, less stromal edema and posterior folds and more stratified and differentiated epithelium than paired corneas stored passively in the same medium.

Aim

To use this model to analyze the respective contribution of corneal(C), limbal(L) and conjunctival(Conj) epithelium in regeneration of corneal epithelium.

Methods

Five pairs of fresh human corneas (body donation to Sciences, death to retrieval time <20 hr) were used. During retrieval, a rim of conjunctiva was left intact. Five models were then built by totally mechanically removing 1, 2 or 3 epithelial population(s): C‐L+Conj+, C‐L‐Conj+, C‐L+Conj‐, C+L‐Conj‐, C‐L‐Conj‐ (control). Corneas were then stored for 1 month in the BR (21 mmHg, 2.5 µl/min of CorneaMax, Eurobio) to allow epithelial regrowth. The epithelia were then examined by immunostaining of flat mounted whole cornea using cytokeratine CK12 (corneal epithelium), CK15 (limbal epithelium) and Hoechst (all cells nuclei). Transparency was assessed by a contrast transmission analyzer.

Results

No epithelium regenerated in the controls. In the 4 other models, the cornea was covered by a multilayered corneal epithelium, even in the C‐L‐Conj+, characterized by expression of K3/K12 and a transparent tissue.

Conclusions

The 3 ocular surface epithelia (comprising the conjunctival one) contain stem‐cells or progenitors able to migrate onto the whole cornea and regenerate corneal epithelium independently of each other. In this ex vivo model of corneas deprived of blood supply and innervation, the neovascularization cannot develop. This suggests that the corneal conjunctivalization characteristic of limbal stem cell deficiency is not due to the absence of a progenitor capable of transdifferentiating into corneal epithelium but mainly to the absence of an anti‐angiogenic barrier.
Preclinical study in a corneal bioreactor of the effectiveness of amniotic membrane of umbilical cord extract (AMUCE) for the treatment of corneal deep stromal ulcerations
Authors: Crouzet Emmanuel , Peyret Benjamin , Caroline Trone Marie , Poinard Sylvain , Garcin Thibaud , Dumollard Jean‐Marc , Barnouin Laurence , Gain Philippe , Thuret Gilles
Published: January 2021

Purpose

Our patented corneal bioreactor (BR) improves the long‐term survival of human corneas ex vivo by restoring intraocular pressure and renewal of storage medium.

Aim

To use the BR to test the efficacy of eye drops containing devitalized ground amniotic membrane of umbilical cord extract (AMUCE) to treat deep stromal ulcerations. AMUCE contains high level of proteoglycans, collagen and physiological growth factors.

Methods

Only pairs of human corneas (with ECD > 800 cells/mm2) were used to obtain best possible controls. They were first stored for 2 weeks into the BR filled with CorneaMax (Eurobio, France), with 21 mmHg in the endothelial chamber to allow regeneration of a normal epithelium. Then, an 8.0 mm diameter calibrated epithelial ulcer was made with a spatula and a 6 mm diameter × 100 µm in depth was made with Excimer laser in the stroma. Using a specific BR lid allowing sterile handling, each cornea was treated topically 4 times daily either by the AMUCE eye drops (TBF, France) or by the vehicle (0.9% NaCl). Closure of the ulceration was monitored daily using fluorescein staining quantified by image analysis (FIJI) of macro‐zoom microscopy. After wound healing corneas were fixed for histology (HES) and immunolabeling of epithelial markers.

Results

Three pairs were used. Epithelium wound healing was obtained at D3, D9, D10 with AMUCE and D3, D9, D19 with the vehicle. Histology performed in ulcerations centre showed 3‐6 epithelial layers with AMUCE and 1‐4 with the vehicle. At D21, significant epithelial detachment was observed only for 2 corneas treated with the vehicle. For one pair, immunolabelling for E‐cadherin and Cytokeratin K3/K12 showed better epithelial differentiation with AMUCE than with vehicle. No evidence of stromal regeneration was observed in the 6 corneas.

Conclusions

AMUCE has potential for a faster and lasting epithelium regeneration (stratification and maturation). Nevertheless, it has no impact on stromal regeneration in this model.
Ultra‐high frequency 70 Mhz ultrasound and IVCM are useful for diagnostic and therapeutic management of atypical Terrien's marginal degeneration
Authors: Caroline Trone Marie , Lise Lanfant , Emera Chhuy , Fabien Forest , Cyril Habougit , Jean‐Luc Perrot , Gilles Thuret , Philippe Gain
Published: January 2021

Purpose

Terrien's marginal degeneration is a rare corneal disease usually characterized by an «insidious thinning of the cornea near the limbus» (Pouliquen Y et al. 1989). Its diagnosis remains essentially clinical.

Aim

To present the help of innovating imaging in an atypical cystic presentation of Terrien's marginal degeneration.

Methods

An 87‐year‐old caucasian patient presented since several month a voluminous cystic lesion of the limbus, bulky, neo‐vascularized, in the inferior part of the eye, that compromised the palpebral closure. No traumatic or surgical history was found. Slit‐lamp examination of the contralateral eye also revealed a degenerative area with corneal thinning. In order to determine the etiology of this lesion, 70 Mhz ultrasound (VevoMD high‐frequency ultrasound system, Fujifilm, Toronto, Canada), anterior segment optical coherence tomography (OCT, Casia 1, Tokyo, Japan) and in vivo confocal microscopy (IVMC, Vivascope 3000, LUCID, NY, USA) were performed. Surgical removal of the lesion consisted of en bloc removal of the cystic lesion followed by limbal conjunctiva and amniotic membrane graft for analgesic purposes and to accelerate wound healing. Histology and direct immunofluorescence were performed.

Results

70 Mhz ultrasonography and OCT revealed a single non‐segmented cyst, without scleral fistula or corneal thinning. IVMC showed a single well delineated cyst with clearly visible distinct partitions with no image in favour of malignancy. No signs of malignancy or ocular pemphigoid were founded by histology. We, therefore, concluded to an atypical presentation of Terrien's marginal degeneration.

Conclusions

The combination of sophisticated imaging like ultra‐high frequency 70 Mhz ultrasound, AS‐OCT and IVCM are necessary for diagnostic and therapeutic management of atypical cornea lesions.
Study of TGFβ‐induced modifications in central and peripheral endothelium of normal corneas
Authors: Aouimeur Inès , Naoki Okumura , Koizumi Noriko , Gain Philippe , Thuret Gilles , He Zhiguo
Published: January 2021

Purpose

TGF‐βs trigger ENdothelial‐Mesenchymal Transition (EnMT) in corneal endothelial cells (ECs) in animal models of endothelial wound healing. All the 3 isoforms of TGF‐β were detected in human aqueous humor and their receptors were detected in ECs. More and more evidence indicated that central and peripheral ECs have a different status.

Aim

To compare the effects of the 3 isoforms of TGF‐β1, 2 and 3 on ex vivo corneal endothelium and to compare their effects on central and peripheral endothelium.

Methods

10 pairs of fresh human corneas (body donation to Sciences) were incubated in a serum free medium for 2 weeks at 31°C. One cornea of each pair was incubated with 10 ng/mL of TGF β1 or 2 or 3, the paired cornea without TGF‐β or with another isoform of TGF‐β (n = 2 for each comparison). Immunolabelling using markers of ECs (ZO‐1, CD166, COX IV and N‐cadherin) and of mesenchymal cells (MCs) (CD44, Collagen 1 and fibronectin) was performed of flat‐mounted corneas. Staining was observed with confocal microscopy to map the regional expression of each marker.

Results

In the controls, MC markers were expressed only by ECs located at the extreme periphery and by trabecular cells. The 3 isoforms of TGF‐β induced the loss of EC markers and the increase of MC markers in central and peripheral endothelium. The effects of TGF‐β1 and 2 were higher than that of TGF‐β3. TGF‐β‐induced alterations were more pronounced in central than in peripheral endothelium.

Conclusions

Normal ECs at the extreme periphery and trabecular cells share characteristics of MCs. These ECs could then derive from trabecular cells. TGF‐β (10 ng/ml) induces EnMT in the center of the endothelium of normal corneas. Physiological concentration of TGF‐β might contribute to maintain peripheral ECs in an undifferentiated state able to slowly proliferate and contribute to endothelial homeostasis.
Retinal microglial activation in a SOD1 mouse model of ALS
Authors: Pilar Rojas Lozano María , Cadena Santoyo Manuel , Fernández‐Albarral José A. , López‐Cuenca Inés , Salobrar‐Garcia Elena , De Hoz Rosa , José Salazar Corral Juan , Luis Urcelay Segura José , Santos‐García Irene , De Lago Eva , Manuel Ramirez Jose , Isabel Ramirez Ana
Published: January 2021

Purpose

To determine the differences in retinal microglial behaviour in a SOD1G93A mouse model (SOD) of amyotrophic lateral sclerosis (ALS) compared to the wild type (WT).

Methods

In retinal whole‐mounts labelled with anti‐Iba‐1 (microglial marker) from two experimental groups WT (n = 6) and SOD ALS (n = 6), signs of microglial activation were quantified in different retinal layers: (i) Iba‐1 + cells number in outer segments (OS), outer plexiform layer (OPL) and inner complex layer (ICL) constituted by inner plexiform layer (IPL), ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL); (ii) cell area of Iba‐1+ cells in OPL and IPL; (iii) arbor area of Iba‐1+ cells in OPL and IPL. Animals were sacrificed with 120 days old.

Results

Compared to WT, the retina of SOD1 ALS mice showed: (i) Migrations and reorientation processes of some Iba‐1 + cells; (ii) A significant increase in the Iba‐1 + cell area in OPL (in inferior, nasal, temporal regions and total number) and in the total number in IPL; (iii) A significant increase in the arbor area in the inferior OPL region; (iv) No significant changes were observed in the number of Iba‐1 + cells in OS, OPL and ICL.

Conclusions

These findings demonstrate a non‐proliferative microgliosis in SOD1‐ALS mice retinas. The microglial activation was higher in OPL, which could be related to an increased inflammatory process in this retinal layer. Although ALS is a motor neuron disease, it can also affect the retinal tissue where an inflammatory process takes place.
New HECplus protocol to further improve the accuracy of pan‐endothelial viability measurement
Authors: Al‐Bourgol Samy , Maurin Corantin , He Zhiguo , Perrache Chantal , Acquart Sophie , Ninotta Sandrine , Forest Fabien , Gain Philippe , Thuret Gilles
Published: January 2021

Purpose

The HEC (Hoechst‐Ethidium‐Calcein) labeling, which we described in 2011, is a simple destructive test unanimously adopted to determine the pan‐endothelial viable endothelial cell density (vECD) using image analysis (e.g. using CorneaJ, ImageJ dedicated plugin). Sometimes, the endothelial surface folded by stromal edema remains difficult to analyze. We present here the HECplus technique, which, with an optimization of image acquisition and analysis, further increases the accuracy of vECD determination, particularly in endothelial folds.

Methods

10 pairs of corneas stored in organoculture at 31°C were analyzed. The endothelial side was incubated with 4 µM Calcein‐AM, 1 µM Ethidium and 11 µM Hoescht 33342 for 45 min at RT. Fluorescence was acquired in 3 channels first with a macroscope, in 3D with an image stacking of the entire graft then with a microscope after flat mounting. A 2 mm plastic pellet emitting constant fluorescence at 510 nm was imaged at the same time to normalize the images. Only one sharp image was reconstructed in ImageJ from the stacks of images. The final standardized images were then analyzed by CorneaJ (HEC group) and then manually by delimiting all viable surfaces on a graphic tablet (HECplus group)

Results

The vECD was significantly higher by 8.2 ± 1.9% in the HECplus group versus HEC (2059 ± 127 versus 1989 ± 156 cells/mm2). Endothelial cells died preferentially in the top of the folds and were better preserved in the bottom of the folds. While HEC wrongly considered some folds as dead, HECplus allowed the error to be corrected. The folding pattern was similar between the 2 corneas of the same pair but differed from one donor to another. The normalization of images for calcein showed overall differences in the level of fluorescence between corneas, suggesting differences in metabolic activity.

Conclusions

We recommend applying the HECplus protocol when a very high degree of accuracy is required, for example when comparing storage media.
The active storage machine (ASM) allows detecting traces of corneal refractive surgery: case report
Authors: Al‐Bourgol Samy , Ninotta Sandrine , Crouzet Emmanuel , Maurin Corantin , Caroline Trone Marie , Garcin Thibaud , Sophie Gauthier Anne , Thuret Gilles , Gain Philippe
Published: January 2021

Purpose

The detection and selection of corneas operated on for refractive surgery (LASIK or photorefractive keratectomy (PKR) by excimer) will become a major concern for eye banks in the coming years because this surgery is often forgotten during the interview with the deceased's relatives. Passive storage in organoculture (OC) prevents the detection of the traces of this surgery because of stromal edema making the cornea less transparent and wrinkled. On the other hand, the active storage machine (ASM) restores intraocular pressure, restores the cornea to its original shape, respects transparency and incorporates non‐invasive controls. It is, therefore, likely to facilitate the detection of refractive surgeries. We present here the case of 2 corneas operated on with PKR and stored successively in OC and ASM.

Methods

The 2 corneas of a 49‐year‐old donor operated 20 years earlier by PKR for ‐2 and ‐3 diopters myopia were stored in OC for 14 days and then placed in ASM for 48 hr. Transparency (transparometer, BiiGC), thickness map and OCT topography (Casia 1, Tomey) were performed under the 2 storage conditions. At the end of the observation, histology and electron microscopy were performed.

Results

Traces of PKR remained unnoticed in OC while they were evident in ASM: central epithelial anomaly, central thinning and flattening of central keratometry were found respectively in transparometry, pachymetry map and OCT topography. Histology and ultrastructure confirmed the absence of Bowman's membrane, pathognomonic of PRK.

Conclusions

By placing the cornea under physiological conditions, and in particular by triggering its deswelling thanks to the intraocular pressure and by restoring its natural curvature, the ASM should allow effective detection of refractive surgery traces.
Visual acuity and contrast sensitivity are slightly modified in young subjects at high genetic risk of developing Alzheimer’s disease
Authors: López‐Cuenca Inés , Elvira‐Hurtado Lorena , Salobrar‐Garcia Elena , Fernández‐Albarral José A. , Lozano María Pilar Rojas , Corral Juan José Salazar , Ramirez Ana Isabel , Ramirez Jose Manuel , De Hoz Rosa
Published: January 2021

Purpose

Alzheimer’s diseases (AD) is the most common cause of dementia characterized by a progressive decline in cognitive function, especially in the memory domain. It is known that its signs can appear decades before to clinical symptoms. In addition to age, genetic studies have identified an association between the presence of the Apoliprotein (ApoE) ɛ4 allele and family history of disease with the late‐onset AD. The aim of the present study was analyzed the possible changes that may occur in visual acuity (VA) and contrast sensitive test (CST) in young subjects with two marked genetic factors risk of developing Alzheimer’s (AD): a first‐degree family history of the disease and being carrier of at least one e4 allele for the ApoE gene.

Methods

A case‐control study was conducted in 28 subjects with family history of AD (FH+), ApoE ɛ4 carriers and with a mean age of 53.39 years and 16 age‐matched control subjects without a family history of AD (FH‐), ApoE ɛ4 non‐carriers and with a mean age of 53.94 years. A complete eye examination was performed in all participants, who were free of ocular pathology.

Results

We found statistical significant increase (p < 0.05) in FH+ ApoE ɛ4 carriers compared to FH‐ ApoE ɛ4 non‐carriers in: I) VA (1.04 ± 0.10, FH+ vs 0.98 ± 0.04, FH‐) and II) CS in the spatial frequency (SF) of 12 cycles/degree (1.68 ± 0.18, FH+ vs 1.54 ± 0.17, FH‐).

Conclusions

In FH+ ApoE ɛ4 carriers, the VA and CST registered changes compared to FH‐ ApoE ɛ4 non‐carriers. In young subjects at high genetic risk of developing AD, an increase of VA and CS in the 12 cicles/degree SF could be the first functional changes to appear.
Innovative ex vivo model of human herpetic keratitis to evaluate antiviral drugs: proof of concept with 0.15% ganciclovir ophthalmic gel
Authors: Courrier Emilie , Maurin Corantin , Bourlet Thomas , Herbepin Pascal , Paul Verhoeven , Gain Philippe , Thuret Gilles
Published: January 2021

Purpose

We have recently developed and characterized a unique model of herpetic keratitis reproducing dendritic or geographic ulceration on human corneas stored in our corneal Bioreactor (BR). The BR is a multi‐application experimentation platform developed to keep the cornea alive for prolonged periods of time in a physiological environment of intraocular pressure and environmental renewal.

Aim

To evaluate whether this model can be used to test the efficacy of antiviral eye drops.

Methods

HSV‐1 keratitis was obtained as previously described: paired corneas discarded from our eye bank were stored in the BR for 14 days (D) at 21 mmHg and 2.6 µl/min of medium renewal (CorneaMax, Eurobio, France) to allow epithelial regeneration. A superficial linear epithelial lesion was then made in the centre, followed incubation of the epithelial surface for 1 hr in a solution of 106 Plaque‐Forming Unit/mL HSV‐1. Three days post‐infection, 0.15% ganciclovir ophthalmic gel used with active molecule at 3.75 µg/ml was instilled on the cornea inside the BR, 3 times/day during 14D and 2 times/day during 5D. The gel was rinsed after 10 min with BSS. The paired cornea was treated similarly with the vehicle (carbomer 974P). Changes in epithelial ulceration size were monitored daily by non‐invasive imaging through the transparent BR windows. Histology and immunolabeling (HSV‐1 gpB, epithelial markers) were done at D40.

Results

For the control corneas, the entire epithelium desquamated at D10. At D40 all keratocytes expressed gpB and endothelial cells partly disappeared. For ganciclovir‐treated corneas, only half of the epithelium desquamated at D14, then it began to regenerate during the third week to reach 1 to 3 epithelial layers at D40. Epithelial and endothelial cells were not infected (gpB‐). Some keratocytes were infected only in the periphery.

Conclusions

Model of herpetic keratitis in the BR has a high potential to evaluate antiviral eye drops efficacy.
Monitoring blood reflux through the trabecular micro‐bypass device “iStent inject”during gonioscopy as a way to follow the patient and optimize the therapy
Authors: Azzawi Abdelwahhab , Sachs Helmut
Published: January 2021

Purpose

A case series of monitoring Blood reflux during Gonioscopy after 3‐6 months of the implantation of the trabecular micro‐bypass device “iStent inject® or iStent Inject W®” with cataract surgery to evaluate the effectiveness of the implantation and adjust the therapy.

Methods

A gonioscopy with Goldmann 3 mirror classic contact lens 903 was performed on 22 eyes after implanting iStent inject® or iStent inject w® combined with cataract surgery. Patients are diagnosed with early primary open‐angle Glaucoma (POAG) or with ocular hypertension (OHT), and they were treated with at least one hypotensive eye drops (ED) before the surgery. The patients were controlled regularly after the surgery, and the therapy was reduced in most cases and adjusted to reach the target pressure according to the guidelines of European glaucoma society with consideration of the IOP before the surgery. The Gonioscopy was performed between 3 and 6 months after the surgery to evaluate the blood reflux through the iStent.

Results

The mean IOP in the patients after the surgery was 18 mmHg with a mean of 1.25 eye drops with no complications, and no patient needed a second surgery. The mean reduction of eye drops (ED) was 1 ED after the surgery. Three of the patients who had IOP less than 15 mmHg had blood reflux through one of the two iStents during Gonioscopy.

Conclusions

Gonioscopy may offer a reasonable and effective method to evaluate the function of iStent after implanting iStent with no extra costs, and it could help in adjusting the therapy after the surgery.
Immunolabelling of usual and putative limbal stem cells markers on flat mounted whole human corneas
Authors: Vaïtinadapoulé Hanielle , Perrache Chantal , Forest Fabien , Marc Dumollard Jean , Gavid Marie , Gain Philippe , Thuret Gilles , He Zhiguo
Published: January 2021

Purpose

The permanent regeneration of the human corneal epithelium involves the proliferation of basal cells of corneal epithelium for compensating for daily desquamation (Majo et al. Nature 2008) and of limbal stem cells (LSCs, Cotsarelis, Cell 1989) located in limbal crypts that can be stimulated in case of important epithelial lesion. Many markers of LSCs had been described in the literature but some are controversial, particularly for their specificity.

Aim

To evaluate the specificity of the main LSC markers proposed in the literature and map their expression on the surface of the cornea.

Methods

Referenced or potential markers of LCSs were tested on cross‐sections of fresh human corneas (body donation to Sciences, time between death‐retrieval‐fixation <21 hr) using a standard technique of immunohistochemistry: ABCB5, ΔNp63, P63, ABCG2, Pax6, CK15, CK17, N‐cadherin, Connexin 43, EGFR, vimentin, Sox2, OCT 4. Secondly, antibodies that showed positivity on cross sections were used for immunolabelling flat‐mounted whole cornea to map their expression.

Results

None of 13 markers was exclusively located at the basal layer of the limbal epithelium. Nevertheless, CK15 appears to be the most promising marker because of its very strong staining in the limbal basal cell layer. However, its staining was also found, less intense, in basal layer of conjunctival epithelium and medium layers of limbal epithelium. On flat‐mounted corneas, CK15 was expressed in a circular ring corresponding to the anatomical limbus, but CK15+ cells were not restricted within the Vogt palisades (or limbal crypts on cross sections).

Conclusions

A marker of cells located exclusively in limbal crypts or Vogt palisades and presumed to be the true LSCs is still missing. CK15 seems the most specific markers for limbal basal cells but not restricted to specific niches.
Prolyl oligopeptidase inhibitor KYP‐2047 alleviates inflammation in retinal pigment epithelium cells
Authors: Toppila Maija , Ranta‐aho Sofia , Bhattarai Niina , Korhonen Eveliina , Hytti Maria , Kauppinen Anu
Published: January 2021

Purpose

Retinal inflammation and dysfunctional protein clearance are characteristics of age‐related macular degeneration (AMD) – the most common cause of blindness in the developed countries. Prolyl oligopeptidase (PREP) is a serine protease that has several functions in the cells including regulation of inflammatory mediators. In this study, we investigated the effects of PREP inhibitor KYP‐2047 on inflammation in retinal pigment epithelium (RPE) cells with blocked proteasomal clearance.

Methods

Proteasomal degradation in ARPE‐19 cells was inhibited by MG‐132. The cells were exposed to the PREP inhibitor KYP‐2047 (1 µM) for 15 min before adding MG‐132 (5 µM) for 6 h or 24 h. Cytotoxicity was determined using the lactate dehydrogenase (LDH) assay. Cytokine levels (IL‐6 and IL‐8) were measured from cell culture medium samples using the enzyme‐linked immunosorbent assay (ELISA) method. Autophagy markers p62/SQSTM1 and LC3 were determined using Western blot technique.

Results

Cells suffering from MG‐132‐induced proteasomal blockade showed higher LDH leakage and IL‐8 secretion as well as accumulation of the autophagy marker p62/SQSTM1 and increased conversion of LC3‐I to LC3‐II. The PREP inhibitor KYP‐2047 reduced the levels of LDH and pro‐inflammatory cytokines IL‐6 and IL‐8 in human RPE cells exposed to MG‐132. KYP‐2047 did not have a significant effect on the levels of autophagy markers at the 24 h time point.

Conclusions

PREP inhibitor KYP‐2047 protects human RPE cells from MG‐132‐mediated cytotoxicity and alleviates inflammation. Further studies are needed to uncover the underlying mechanism, but PREP inhibition is a promising therapy target in AMD.
Endothelial viability after DSAEK cutting of corneas stored in Tissue‐C organoculture medium and deswelled in Carry‐C medium (Alchemia)
Authors: Vaïtinadapoulé Hanielle , Al‐Bourgol Samy , Ninotta Sandrine , Theilliere Christian , Gouttefange Catherine , Acquart Sophie , Thuret Gilles , Gain Philippe
Published: January 2021

Purpose

In France, the adoption by an eyebank of a new technique for graft preparation and/or a new CE‐marked storage medium requires the submission of a “process” file to the competent health authority. This file must include pre‐clinical data on corneas stored in this medium or prepared with the new technique.

Aim

To analyze the endothelial alterations induced by the pre‐cutting with the microkeratome of corneas stored in Tissue‐C organoculture medium and deswelled in Carry‐C medium.

Methods

Ten pairs of corneas (donation for scientific purposes) were retrieved by in situ corneo‐scleral cutting and immersed in 100mL of Tissue‐C (Alchemia, Italy) and stored at 31°C in a dry incubator for 30 days (D). At the beginning (D2 to D5) and end (D30) of storage, the usual quality control was performed: central endothelial cell density (ECD) after incubation with 0.9% NaCl, transparency, thickness (OCT) and microbiological control. At D30, the corneas were transferred to a deswelling Dextran‐containing medium (Carry‐C, Alchemia) for 24 H. After randomization, one cornea of each pair was pre‐cut with the MORIA linear microkeratome (DSAEK, single pass, objective #150 µm) and put back in Carry‐C for 72H. The endothelial viability (viable ECD) of the all corneas was then measured by triple Hoechst‐Ethidium‐Calcein‐AM staining as we previously described (IOVS2011, Cornea2014).

Results

The initial ECD was 2401 ± 815 for the DSAEK group and 2298 ± 805 cells/mm2 for the control group (p = 0.386) and at D30, respectively, from 1945 ± 587 versus 1868 ± 577 cells/mm2 (p = 0.421). One cornea was perforated. Graft thickness was 187 ± 112 um. For the other 9 pairs, the viable ECD (by definition always lower than bank ECD) was 1061 ± 448 for the DSAEKs and 1149 ± 409 cells/mm2 for the controls (p = 0.066). The pre‐cut grafts had fewer endothelial folds.

Conclusions

Pre‐cutting by bank of corneas stored in Tissue‐C/Carry‐C does not induce significant additional cell loss compared to control.
Automated macular segmentation in compressive optic neuropathy and glaucomatous optic neuropathy
Authors: Machado Soares Ricardo , Braga Joana , Da Silva Fernandes Joana , Alves Hélio , Ribeiro Lígia , Meira Dália
Published: January 2021

Purpose

Compressive optic neuropathy (CON) can sometimes mimic glaucomatous optic neuropathy (GON), leading to inadequate management. Our purpose was to compare the macular area of patients with CON and GON to healthy controls (HC) and to determine if the macula area was able to distinguish between CON and GON.

Methods

Retrospective, observational, cross‐sectional study, enrolling 70 patients (22 patients with CON, 25 with GON and 23 HC). Subjects were matched by age (median of 61 [±11.6]), and one eye was randomly selected. Spectral‐domain optical coherence tomography (SD‐OCT) images were generated using the Spectralis® OCT device (Heidelberg, Germany). An automated algorithm was used to segment the macular retina into nine layers and evaluate the thickness of each layer in the foveal, inner, and outer Early Treatment Diabetic Retinopathy Study (ETDRS) subfield rings. Data were compared across all study groups using Kruskal‐Wallis test, followed by pairwise comparisons for each duo. The resulting p‐values were adjusted using the Bonferroni correction and significance level was set at 0.05.

Results

HC had thicker inner retinal layer (IRL) compared with GON and CON (p < 0.05). Global retinal thickness was significantly thinner in the inner superior (IS) and inner nasal (IN) subfields in CON compared with GON (p < 0.05). The IRL is thinner in CON, specifically in the inner and outer nasal subfields, compared to GON. The IN subfield was thinner in the retinal nerve fibre, ganglion cell and inner plexiform layers (IPL) in CON compared with GON (p < 0.05). No differences were found on the inner nuclear, outer plexiform, outer nuclear and outer retinal layers between groups.

Conclusions

Our findings suggest that IRL is thinner in both CON and GON, and the IN subfield is specially affected in CON compared with GON. Despite not being our primary outcome, our results suggest that, compared to HC, layer neurodegeneration in both CON and GON affects mainly the inner layers and that does not extend to layers external to IPL. In conclusion, evaluation of the macular segmented layers damage, by SD‐OCT, may be a useful add‐on tool in the differential diagnosis between these two entities, when their manifestations overlap.
Visual impairment and associated risk factors among school‐age children in Kashatagh, Artsakh
Authors: Giloyan Aida , Harutyunyan Tsovinar , Petrosyan Varduhi
Published: January 2021

Purpose

Visual impairment in childhood can have a profound impact on child's development, restricting social life and limiting physical and educational opportunities. This study assessed the prevalence of visual impairment and associated risk factors among school‐age children living in Kashatagh, Artsakh.

Methods

The researchers recruited 454 school‐age children from seven urban/rural schools in 2016. The structured questionnaire included questions about socio‐demographics, frequency of visiting ophthalmologist, ocular health and vision acuity. All children underwent a detailed ophthalmic examination including measurement of visual acuity, cycloplegic refraction and dilated eye fundus examination. Visual impairment was defined by a presenting visual acuity <6/12 with or without correction in the better eye. Descriptive statistics and logistic regression were used to analyze the data.

Results

Children's mean age was 11.1 (3.28), ranging from 6 to 19 years. About 55% participants were girls. The majority of children never visited ophthalmologist (86.1%). The prevalence of presenting visual impairment without correction and with available correction in the better eye were 6.0% and 4.6%, respectively. After best correction, all visually impaired cases improved their vision to ≥6/12. The majority of visually impaired participants had myopia (55.6%). In the adjusted analysis, age (OR = 1.22; 95% CI: 1.04–1.44), female gender (OR = 3.33; 95% CI: 1.07–10.3) and frequency of visiting an ophthalmologist (OR = 11.8; 95% CI: 4.35–32.2) were associated with presenting visual impairment without correction. Visually impaired children more frequently visited an ophthalmologist compared to those with no visual impairment.

Conclusions

Correctable visual impairment is a major problem in this sample. All visually impaired cases improved their vision to ≥6/12 after best correction in the better eye. School‐based vision screening programs and provision of spectacles can decrease visual impairment in school‐age children.
Epidemiological analysis of conjunctival lymphoma: a population‐based study, 2000–2016
Authors: Mikhael Sandra , Tadrosse Abanoob , Yassa Arsany , Mikhael Mina , Eloy Jean‐Anderson
Published: January 2021

Purpose

To study epidemiological trends of conjunctival lymphoma.

Methods

A retrospective, population‐based analysis of patient data extracted from the Surveillance, Epidemiology, and End Results Registry US database was conducted from 2000 to 2016. Incidence (IR) was calculated in number of cases/million/year. Disease‐specific survival (DSS) was calculated using the Kaplan‐Meier method.

Results

978 cases of conjunctival lymphoma (CL) were identified, of whom 52% were females and 65% were white. The most common histological subtypes were mucosa‐associated lymphoid tissue (MALT; 70.9%) and follicular lymphoma (11.7%). Diffuse large B‐cell lymphoma constituted only 3.4% of cases. Overall IR of CL was 0.7. Annual percent change showed a significant decline (−1.4) in IR of CL during 2000–2016 (p = 0.02). There was no difference in IR between sexes (p = 0.34). IR in Asian/Pacific Islander patients (0.9) was significantly higher than that in white (0.6) and black (0.5) [p < 0.01] patients. Mean diagnostic age in years was 59.3 [Standard Deviation = 17.9]. IR in patients older than 65 years old (y/o) [2.36] was significantly higher than that in those 22–64 y/o (0.63; p < 0.01) and those younger than 21 y/o (0.06, p < 0.01). IR of unilateral cases (0.6) was significantly higher than that of bilateral ones (0.1) [p < 0.01] and there was no significant difference between left and right laterality (p = 0.72). 5‐year DSS during 2000–2012 was 97.4%. Race and sex did not affect survival. DSS was similar during 2010–2012 (98.5%) and 2000‐02 (94.1%) [p = 0.099].

Conclusions

Conjunctival lymphoma incidence is highest in the elderly and Asian/Pacific Islander populations and is not affected by sex. Incidence is decreasing over the timeframe 2000‐2016. Most common histology for CL is MALT. Overall 5‐year DSS for CL is 97.4%, and it is not affected by sex or race.

Bibliography

Surveillance Research Program, National Cancer Institute SEER*Stat software (seer.cancer.gov/seerstat) version 8.3.6.
Spontaneous corneal perforation in a young patient with vernal keratoconjunctivitis
Authors: Reinhold Aja , Baston Arthur , Della Volpe Maria , Janeschitz‐Kriegl Lucas , Traber Ghislaine , Scholl Hendrik , Gkatzioufas Zisis
Published: January 2021

Purpose

Spontaneous corneal perforation is a rare complication of systemic diseases with ocular involvement such as Sjögren's syndrome, rheumatoid arthritis, graft‐versus‐host disease or ocular rosacea. There are few cases of spontaneous perforations in adult patients described in the literature associated with keratoconus (KC) or pellucid marginal degeneration (PMD). This case describes a spontaneous corneal perforation in a young patient with vernal keratoconjunctivitis.

Methods

Case report.

Results

A 14‐year‐old male patient presented at the Department of Ophthalmology accompanied by his parents due to one day existing redness and hazy vision of the left eye (OS). Additionally, he noticed a sudden “water outflow from the left eye.” The patient's medical history includes vernal keratoconjunctivitis, systemic prediabetes, obesity and steatohepatitis. Slit‐lamp examination of the left eye revealed a spontaneous corneal perforation of 1.4 × 1.8 mm inferonasal with iris tamponade and a surrounding corneal melting of 4 mm. The anterior chamber had been totally flattened. The right eye was diagnosed by slit‐lamp examination with central corneal thinning and inferior peripheral vascularization. The corneal perforation was primarily treated with histoacrylic tissue glue. Antibiotic treatment with Ceftazidime and Moxifloxacin eye drops alternating every hour has been established. After one week, a progressive corneal melting in the area of the primary corneal perforation was observed. Therefore, a patch “keratoplasty à chaud” had to be performed. The postoperative course was devoid of complications. The patient was initially treated with Pred forte eye drops 4 times daily. An optical penetrating keratoplasty is planned.

Conclusions

Spontaneous corneal perforation is an extremely rare but severe complication of vernal keratoconjunctivitis, which can also occur in young patients. Ophthalmologists should be aware of this rare complication and inform and treat their patients accordingly.
Assessing clinical evidence for idebenone in the treatment of chronic Leber Hereditary Optic Neuropathy: a systematic literature review
Authors: Carlot Sara , Amadasi Alessio , Bianchi Francesco , Lloria Xavier
Published: January 2021

Purpose

Leber Hereditary Optic Neuropathy (LHON) is a mitochondrial genetic disorder causing severe, bilateral loss of visual acuity (VA). Idebenone is the only treatment for LHON currently approved in Europe. Due to the rarity of the disease, information about outcome in patients starting treatment >12 months since disease onset in the most recent eye (chronic LHON) is scarce.

Methods

The search for clinical evidence included any published study or conference abstract evaluating oral idebenone at the approved dose of 900 mg/day, in patients with confirmed diagnosis of LHON starting treatment >12 months since disease onset in the most recent eye. Literature search was carried out on Medline, Embase, InsightMeme and Cochrane Libraries up to March 2020.

Results

Evidence for idebenone treatment of chronic LHON is based on four uncontrolled, retrospective case series and one post‐hoc analysis of a randomized controlled study. All studies included patients (n = 4–53) with confirmed primary LHON mutations and evaluated changes in VA with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The post‐hoc analysis (n = 53, idebenone:34; placebo:19) assessed efficacy as rate of clinically relevant recovery (CRR; defined as improvement from off‐chart to reading five letters, or improvement of 10 letters) from baseline (BL) after 6‐month therapy. 35.3% of idebenone‐treated versus 10.5% of placebo patients achieved CRR (p = 0.059); by eyes: 23.5% versus 5.3% (p = 0.016). All 4 retrospective studies (n = 4–16) assessed efficacy as average VA improvement (all eyes) from BL after 9 to 12 months of therapy. Improvements ranged from −0.20 to −0.31 logMAR (2–3 ETDRS lines). One retrospective study compared the effect of idebenone in two subgroups according to time from LHON onset (1–5 years, n = 7; >5 years, n = 8) showing no difference between groups.

Conclusions

Data presented indicates a potential therapeutic effect of idebenone in chronic LHON patients, which may be explained by the reactivation of dysfunctional retinal ganglion cells and deserved further investigation.
Light‐field imaging for glaucoma diagnosis—reproducibility on one patient
Authors: Dietzel Alexander , Schramm Stefan , Link Dietmar , Klee Sascha
Published: January 2021

Purpose

A suspicious optic nerve head appearance with abnormal cupping or increased cup‐to‐disc ratio is considered as a strong risk factor for glaucoma. Typical systems to measure this deformation are optical coherence tomography or scanning laser ophthalmoscopy. We show that the needed depth information for glaucoma diagnosis can be obtained reliably with a commercial fundus camera using an adapted light‐field camera providing a one‐shot 3d retinal image.

Methods

We examined the left eye of a glaucoma suspect (male, 39 years) 11 times in compliance with the Declaration of Helsinki. For each examination, the glaucoma suspect repositioned himself and the device was readjusted. The images were taken with a fundus camera (FF450, Carl Zeiss Meditec AG) combined with a modified light‐field camera (Raytrix R12, Raytrix GmbH). The eye was illuminated with a wavelength of 520 nm (±20 nm). The absolute virtual depth (VD) values were exported from the Raytrix software (RxLive 5.0, Raytrix GmbH) and further processed in Matlab R2018. All data were aligned to each other to measure at similar locations. The maximum VD on a vessel segment above the rim and the minimum above the root of the vessel inside the optic nerve head was determined to calculate the depth difference.

Results

All images showed a clearly identifiable optic nerve head structure and allowed a successful and reliable determination of the depth information. The average relative depth difference over all examinations was 6.1 ± 0.34VD. The 95% confidence interval was between 5.86 and 6.34VD. Besides the depth values also the lateral values are virtual because of an aperture mismatch between fundus camera and light‐field camera. A successful depth estimations of the Raytrix software require high contrast images with textures. Caused by the objective of the fundus camera image distortions existed.

Conclusions

The presented results from our preliminary system show the potential of the light‐field technique to be used for glaucoma diagnostics and progression analysis based on the optic nerve head in 3D. Reliable and reproducible measurements of this technique can enhance the informative value of the classical fundus photography.