bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological changes in retinal layers thicknesses measured with swept source optical coherence tomograph
Authors: Velilla Javier Pérez , Vicente Maria José , Palomar Elisa Viladés , Hospital Elvira Orduna , Palomar Amaya Pérez Del , Banzo Jose Cegoñino , Marco Alberto Montolio , Palacián Maria Satué , Martín Elena García , Ciordia Beatriz Cordón
Published: December 2019

Purpose

To evaluate the physiological changes of the different layers of the retina measured by the standard protocol and the grid points of the swept source optical coherence tomography (SS‐OCT).

Methods

A total of 463 eyes divided into four groups will be analyzed: Group 1 (71 eyes of subjects of 20 and 34 years); Group 2 (65 subjects from 35 to 49 years), Group 3 (with 230 subjects from 50 to 64 years) and Group 4 (97 subjects from 65 to 79 years). Wide protocol of Triton SS‐OCT (Topcon Corporation, Japan) was used to measure thickness of different layers of the retina, retinal nerve fiber layer (RNFL), ganglion cell layer, and choroid.

Results

Transition from group 2 to group 3 showed the most significant thinning of all the retinal layers, especially in the superior‐temporal quadrant of RNFL, ganglion cell and retinal layers (p < 0.001), and temporal sectors in the choroid layer (p < 0.001). A significant RNFL thickening was found in group 2 compared with group 1 in the superior temporal quadrant (p = 0.001), inferior half (p < 0.001) and temporal half (p = 0.001), and also in the choroid layer (p = 0.001).

Conclusion

There is a progressive and physiological thinning of all the layers of the retina from the third decade of life.
Corneal crosslinking for therapy‐resistant keratitis with corneal melting; it is never too late!
Authors: Germann Ursula , Gkatzioufas Zisis
Published: December 2019

Purpose

To report the use of corneal crosslinking (Dresden protocol) as adjuvant treatment in a patient with advanced therapy‐resistant keratitis complicated with corneal melting.

Methods

Case report and literature review.

Results

A 52‐year‐old female patient, who presented with an extended central corneal ulcer and hypopyon, was treated with fortified antibiotic eye drops (Ceftazidin 5% and Moxifloxacin alternating hourly). Corneal cultures were positive for Streptococcus dysgalactiae. On clinical suspicion of fungal co‐infection, treatment was supplemented with Voriconazole eye drops 8 times/day. Two weeks later, Alternaria spp. was detected in corneal cultures. Despite broad‐spectrum therapy, the corneal ulcer progressed and corneal melting occurred. After discussion with the patient we decided to proceed to a corneal crosslinking, before considering therapeutic corneal transplantation. Postoperatively, the corneal melting was reversed and the infection was adequately controlled with formation of corneal scarring.

Conclusion

Corneal crosslinking was successfully implemented to manage corneal melting and control infection in a patient with advanced therapy‐resistant keratitis. Physicians should not ignore the clinical signs of mycotic co‐infection in their clinical assessment, even in the absence of initial positive cultures, and they should consider corneal crosslinking even in advanced corneal ulceration with melting.
An evaluation of complication rates in patients undergoing the unconventional “standing” phacoemulsification procedure
Authors: Mathews Namita , Ebbs Samuel , Tahhan Mazen
Published: December 2019

Purpose

A large proportion of the elderly find lying flat for cataract surgery difficult due to mechanical back issues or medical comorbidities. The “standing” phacoemulsification procedure is carried out with the surgeon standing throughout. Consequently, it allows the patient to have their head and neck elevated to a more comfortable position. This study evaluates the rate of intra‐ and post‐operative complications in patients undergoing this technique.

Methods

Data was collected via the Medisoft database of standing phacoemulsification procedures from January 2012 to October 2018 across two sites in Sandwell and West Birmingham Trust. Complication rates and pre‐ and post‐operative visual acuity were recorded.

Results

Seventy‐five eyes (36 left and 39 right) were included in the study; 60 females and 15 males. The median age of patients was 85 years. There were four recorded intra‐operative complications (5.3%) of which three were recorded with post‐operative complications. Two patients without intra‐operative complications were recorded with a post‐op complication. 55 events had a pre‐ and post‐operative vision recorded of which 74.5% had an improvement in visual acuity, 21.8% remained the same and 3.6% had a deterioration. The rate of posterior capsule rupture was 1.3%.

Conclusion

Our data shows low level of complication rates and improvement in visual acuity remains high. In comparison to the 2016/17 National audit data our Posterior Capsule rupture rate is similar ‐ 1.4% nationally.[1] In conclusion, standing phacoemulsification can be deemed safe however we would need a higher volume of data and follow up to further assess this.

Reference

Donachie P & Sparrow J (2018): . [online] Royal College of Ophthalmologists. Available at: https://www.nodaudit.org.uk/u/docs/20/avusuryktz/NOD%20Audit%20Annual%20Report%202018.pdf. (Accessed 11 Apr 2019).
Hsa‐miR‐150‐5p regulates human corneal epithelial stem cells through Wnt signaling
Authors: Kalaimani Lavanya , Devarajan Bharanidharan , Prajna Namperumalsamy Venkatesh , Veerappan Muthukkaruppan , Daniels Julie T. , Priya Chidambaranathan Gowri
Published: December 2019

Purpose

The aim of this study was to understand the molecular regulatory function of hsa‐miR‐150‐5p in association with the maintenance of stemness in corneal epithelial stem cells (CESCs).

Methods

Small RNA sequencing identified hsa‐miR‐150‐5p to be highly expressed in enriched CESCs compared to central corneal epithelial cells (CCECs). The validation of differential expression of hsa‐miR‐150‐5p in enriched CESCs in comparison to CCECs was carried out by quantitative real time PCR (Q‐PCR) and by locked nucleic acid in‐situ hybridization (LNA‐ISH) in human corneo‐limbal cryosections. Primary cultured limbal epithelial cells were transfected with hsa‐miR‐150‐5p mimic, inhibitor and scrambled sequence (25 nM) using lipofectamine 3000. The transfected cells were analysed for (i) colony forming potential (ii) expression of stem cell markers (ABCG2, NANOG, OCT4, KLF4 and ΔNP63), differentiation marker (connexin‐43) and the hsa‐miR‐150‐5p predicted targets (JARID 2, AKT 3, INHBA and CTNNB1) by Q‐PCR and (iii) expression of ABCG2, p63, connexin‐43, JARID 2, AKT 3 and catenin by immunofluorescence staining.

Results

The expression of hsa‐miR‐150‐5p was higher (13.86±1.5) in enriched CESCs compared to CCECs by Q‐PCR analysis. Hsa‐miR‐150‐5p had relatively higher expression in clusters of cells in limbal basal epithelium compared to other layers by LNA‐ISH. Ectopic expression of miR‐150‐5p increased the colony forming potential (8.28 ± 0.33%) with the ability to form holoclones in comparison to inhibitor treated (0.71 ± 0.10%) and control (1.8 ± 0.15%). The mimic treated cells had higher expression of stem cell markers but reduced expression of connexin‐43 and hsa‐miR‐150‐5p targets involved in Wnt signaling pathway.

Conclusion

A regulatory role for hsa‐miR‐150‐5p in maintenance of stemness by inhibiting Wnt signaling pathway is thus indicated.
Unexpected visual acuity loss as the first sign of a xen implant complication
Authors: Monzón Sara Marco , Sangros Isabel Lopez , Riegel Gisela Karlsruher , Rodriguez Paula Montes , Barreda Maria Dolores Diaz , Murillo Ana Boned , Morales Juana Martinez , Puyuelo Javier Ascaso
Published: December 2019

Purpose

Minimally invasive glaucoma surgery (MIGS) using diferent devices is a promising strategy for treating mild glaucoma. However, long‐term complications require further evaluation. We report a case of displacement to the anterior chamber and cornea of a previously successful XEN implant.

Methods

A 85‐year‐old female treated for open angle glaucoma with Latanoprost, Timolol and Brinzolamide started presenting IOP of 24 mmHg in her right eye and a progression was also evident in visual field examination and spectral‐domain optical coherence tomography. Due to failure of medical treatment, surgery with a XEN implant was offered to the patient. The XEN implant was successfully implanted in the right eye and an adecuate control of the IOP was achieved for eight months. After that period of time, IOP raised to 22 mmHg and topical treatment with Brinzolamide and Timolol was reintroduced. Nine months later, the patient suffered a visual acuity loss and came to the emergency department. During the slit‐lamp examination intense corneal edema, Descement membrane folds and a dislocation of the XEN implant into the anterior chamber affecting the cornea were described.

Results

Taking into account the patient situation we started adding topical corticosteroid therapy to her previous treatment. Finally a surgical removal of the implant was performed. Rejecting other surgical therapies for now, the patient is at the moment treated topically.

Conclusions

Despite MIGS is a safe and useful technique, long‐term complications require further evaluation. We describe the dislocation of a XEN implant into the anterior chamber or to the cornea as a new potential complication of this device to keep in mind.
Clinical validation trial of Glaucoma Easy Screener (GES) as a low‐cost and portable visual field screening tool
Authors: Nida Esmael Kedir , Vandewalle Evelien , Van Keer Karel , Vanden Abeele Vero , Geurts Luc
Published: December 2019

Purpose

The aim of this study is to compare the performance of Glaucoma Easy Screener (GES), as a low cost and portable visual field screening tool to the glaucoma screening test (GST) from Octopus.

Methods

GES is comprised of a Moto G5 smartphone, Homido v1 virtual reality headset and a gaming joystick for user input. The screening app’s design is based on the recently introduced Octopus GST perimeter. The test contains 28 points in the central 300. Test stimuli at each location are presented at an intensity level that can be detected in 95% of the time in case of a normal visual field. The app monitors false positive errors with catch trials and fixation losses using the blind spot method. Test result is presented with a plot of seen and missed points along with other parameters including test duration and reliability indices. A normative database for the GES was constructed by testing 62 eyes of 33 normal subjects (aged 22–56, 10 male/23 female) using a threshold procedure. To evaluate agreement between Octopus GST and GES, 36 eyes of 18 subjects (among the 33 normal subjects) were tested both with GES and Octopus GST.

Results

There is a good level of agreement between Octopus GST and GES, with 31 eyes(86%) showing above 85% agreement, based on the count of seen and missed points. There was above 85% agreement for 24 points in all eyes. The remaining 4 points had an agreement between 78 and 85%. Test duration was slightly higher for GES with an average of 2 min per eye compared to 1.1 min with Octopus GST.

Conclusions

Results from this clinical trial show a good level of agreement between GES and Octopus GST. GES can serve as a low‐cost and portable visual field screening kit to complement other glaucoma tests, to make referral decisions in situations where standard equipment is not available.
Progression patterns of normal‐tension glaucoma groups classified by Hierarchical cluster analysis
Authors: Song Park Hyo , Woo Kim Eun , Keum Park Cham , Choi Wungrak , Hyun Lee Kwang , Je Seong Gong , Yun Kim Chan , Yeop Lee Sang , Won Bae Hyoung
Published: December 2019

Purpose

To investigate differences in progression patterns of normal‐tension glaucoma patients in three clusters classified by Hierarchical cluster analysis (HCA).

Method

200 eyes of NTG patients classified by HCA in 2015 who were followed up until now were included. We evaluated the progression rate of NTG in SD‐OCT and visual field test and compared characteristics of the progression in each group.

Result

A total of 153 patients were followed up and the mean observation period was 5 years. In cluster 1, which showed early glaucomatous damage in the previous report, the mean retinal nerve fiber layer (RNFL) reduction rate was −0.83 μm/year. In cluster 2, which showed moderate glaucomatous damage, the reduction rate was −0.45 μm/year, and In cluster 3, which showed young and myopic glaucomatous damage, the rate was −0.36 μm/year. The progression pattern of cluster 3 showed a double‐peak distribution with the RNFL reduction rate being 0.11 μm/year in non‐progressive group and −1.07 μm/year in progressive group.

Conclusion

When the optic nerve head parameters were classified by HCA, the divided groups showed different patterns of NTG progression. In particular, the group of young myopia showed a mixture of two different patterns. /
In vitro evaluation of cytotoxic potential associated to antimicrobial agents commonly used in clinical ophthalmological practice
Authors: Viola Santa , De Pasquale Giuseppe , Zappulla Cristina , Cristina Curatolo Maria , Grazia Mazzone Maria , Giuliano Francesco
Published: December 2019

Purpose

Topical antibiotics may cause cytotoxic effects on eye surface, especially when the integrity of ocular epithelia is a major concern (e.g. corneal damage). Here we investigated the potential cytotoxicity of one antiseptic (povidone‐iodine) and three antibiotics commonly used in ophthalmology (netilmicin, levofloxacin and chloramphenicol).

Methods

Human Corneal Epithelial cells (HCE) were exposed to all compounds (1.5, 3 or 6 mg/ml) for different lengths of time, i.e. 0.5, 1, 3, 6 and 24h. Cell viability was then assessed by MTT assay. Cell viability cut‐off was fixed at 50% (DB‐ALM: Protocol n°17). Statistics were by two‐way ANOVA.

Results

None of the compounds tested at 1.5 mg/ml had any significant cytotoxic effect, except for levofloxacin producing a 66% cell mortality at 24h. At 3 mg/ml, in addition to levofloxacin, chloramphenicol too produced a submaximal cytotoxic effect at 24h (76%). Netilmicin was the only to be devoid of any cytotoxic effect at 6 mg/ml while all the other compounds produced significant cytotoxic effects with varying onset times, chloramphenicol and povidone‐iodine showing the earliest onset (see figure).

Conclusions

Results demonstrate that levofloxacin and chloramphenicol produce cytotoxic effects on HCE even at concentrations that are lower than those used in clinical ophthalmological practice. Conversely, povidone‐iodine only showed cytotoxic effects at 6 mg/ml, that is the concentrations of eye drops available on the market. Most importantly, netilmicin was found to be endowed with an advantageous cytocompatibility profile being devoid of any cytotoxicity even at concentration exceeding those currently used in clinical ophthalmological practice (3 mg/ml). Further studies are warranted to investigate the potential cytotoxic effects of antimicrobial agents tested in a pulsed‐treatment setup in order to mimic the human dose regimen thus accounting for potential biases due to prolonged cell exposure.
Involvement of innate immunity in the course of choroidal neovascularization in mice
Authors: Kokona Despina , Tsioti Ioanna , Schwarzer Petra , Zinkernagel Martin S.
Published: December 2019

Purpose

To investigate the effect of retinal microglia depletion, and the effect of systemic lipopolysaccharide (LPS) exposure, in the course of laser‐induced choroidal neovascularization (CNV) in mice.

Methods

For microglia depletion, C57BL6/J mice were kept under a diet containing the colony‐stimulating factor 1 receptor (CSF‐1R) inhibitor PLX5622, for 1 week prior to CNV induction and until the end of the experiments. To evaluate the effect of systemic LPS challenge on the CNV course, LPS (1 mg/kg) was given intravenously in control‐fed mice for 1 or 4 consecutive days, immediately after CNV. Mice were imaged with optical coherence tomography (OCT) and fluorescein angiography (FA) at baseline, and at day 3, 7 and 14 after CNV. CNV lesions were measured in the FA images and flow cytometry was used to investigate the effects of PLX5622 on the innate immune cell populations in the retina and the choroid‐RPE of CNV‐subjected mice.

Results

PLX5622 led to microglia depletion in the retina, reduced numbers of dendritic cells, macrophages and leukocytes in the choroid‐RPE and a faster involution of CNV. Retinal swelling, vasodilation and accumulation of microglia/macrophages around retinal vessels were observed at day 4 after the first LPS challenge but not 1 day after a single LPS injection. Moreover, a single LPS injection led to exacerbation of the CNV lesion, while 4 consecutive LPS injections did not affect the CNV size compared to non‐injected mice.

Conclusions

The data suggest that suppression of the ocular innate immune response leads to a faster involution of CNV, while activation of innate immune cells with an acute systemic inflammatory stimulus results in increased CNV areas and slower involution. Moreover, chronic systemic LPS exposure do not affect the course of CNV. These findings highlight the importance of innate immunity in the course of experimental CNV and the different effects of acute and chronic systemic inflammation in the diseased retina.
Disease etiology‐based design of multifunctional trehalose emulsion eye drops for moderate or severe dry eye: a randomised, quadruple‐masked and active‐controlled clinical trial
Authors: Kaarniranta Kai , Järvinen Riikka , Wylegala Edward , Laihia Jarmo
Published: December 2019

Purpose

To assess the safety and efficacy of multi‐ingredient trehalose emulsion eye drops (TEED) designed to target (1) tear film instability, (2) tear hyperosmolarity, and (3) ocular surface damage and inflammation in moderate or severe dry eye.

Methods

This randomised, quadruple‐masked, active‐controlled parallel study in 64 adult patients comprised three parts. Part 1 (n = 3): One eye was treated with TEED for one day. Part 2 (n = 9): Randomised eyes were treated with TEED and 0.2% hyaluronic acid (HA) control eye drops 3 times a day for 10 days. Part 3 (n = 26 + 26): Randomised treatment was applied on both eyes 3 times a day for 30 days. Ocular assessments were performed at baseline and after the last dose.

Results

Both treatments were well tolerated without adverse device effects. Tear film break‐up time (p = 0.0025) and ocular protection index (p = 0.0026; change vs. HA, p = 0.047) increased significantly with TEED after 30 days. Tear osmolarity decreased more in TEED than in HA group and significantly with both eye drops in hyperosmolar subgroups. Corneal (p = 0.014) and nasal conjunctival staining (p = 0.043) were reduced with TEED in per‐protocol patients (n = 24). Conjunctival (p = 0.001) and lid redness (p = 0.012) decreased with TEED in all patients (n = 26). Symptoms decreased by about 25 OSDI units with both treatments (p < 0.0001).

Conclusions

TEED proved safe and efficacious in improving each etiologic factor for dry eye. Hyperosmolar stress dominating blink cycles must be disrupted by biophysical protection of the ocular surface to facilitate resolution of cellular damage and inflammation, and relief of ocular symptoms.
Microglial analysis in whole‐mount retina of Alzheimer's disease 3xTg‐AD mouse model
Authors: Ramírez Ana I. , Salobrar‐García Elena , Rodrigues‐Neves Ana C. , de Hoz Rosa , Salazar Juan J. , Fernández‐Albarral José A. , López‐Cuenca Inés , Rojas Pilar , Ambrósio Antonio F. , Ramírez José M.
Published: December 2019

Purpose

Alzheimer’s Disease (AD) is a primary degenerative disease that is characterized by the accumulation of β‐amyloid and tau in central nervous system, even in visual brain areas and in the retina. This raises the possibility that tracking changes in the retina can be used to assess neurodegeneration in AD.

Methods

We analysed the retinas of 16‐month‐old 3xTg‐AD transgenic mice, which are used as an animal model of AD, and wild‐type (C57BL6/129S). Whole mount retinas were stained with antibodies against Iba‐1 and OX‐6. The morphology, number and soma size of microglia in the retina were analysed.

Results

Retinas from 3xTg‐AD transgenic mice showed signs of microglial activation relative to retinas from wild‐type animals: greater number of microglia, thickening of microglial soma, retraction of microglial processes and migration of microglia within and between layers. This activation was associated with alterations in the microglial plexus in the external plexiform layer and in the complex of internal layers. Retinas from 3xTg‐AD mice showed circular groups of microglia that reoriented and polarized their processes differently than in control retinas. Moreover, it was found a significant increase in both the number and cell body area of Iba‐1+ cells in 3xTg‐AD retinas in comparison with wild‐type retinas.

Conclusions

Retinas from a mouse model of AD show signs of microglial activation. Reactive gliosis caused by AD‐associated protein aggregation may trigger morphological changes in the retinas of AD patients.

Acknowledgments

Santa Casa Mantero Belard Award 2015 (MB‐1049‐2015), Foundation for Science and Technology (PEst UID/NEU/04539/2013), COMPETE‐FEDER (POCI‐01‐0145‐FEDER‐007440), and Centro 2020 Regional Operational Programme (CENTRO‐01‐0145‐FEDER‐000008: BrainHealth 2020).
Study about the association between diabetic macular edema and avascular foveal area, diameter and thickness of the superficial and deep retinal plexuses
Authors: Montes Paula , Karlsruher Gisela , Boned Ana , Dolores Díaz María , Marco Sara , López Isabel , Esteban Olivia , Javier Ascaso Francisco
Published: December 2019

Purpose

Our objective is to study in diabetic patients if there is an association between the presence of macular edema (diffuse or cystic) or not and the area of the foveal avascular zone (ZAF) in the superficial and deep retinal plexuses, diameters and the macular thicknesses measured with OCT and OCT‐A.

Methods

We performed a retrospective observational study with 13 diabetic patients (26 eyes). We have extracted general data of its history, characteristics about the evolution of its disease and ocular affectation, such as sex, age, time of evolution of diabetes, presence of diabetic retinopathy or not, treatments received and visual acuity. In each patient, on two images of OCT angiography (superficial plexus and deep plexus), we measured (with the “Triton” software) the area of the ZAF, as well as the larger diameter. In the classic OCT we have determined the central macular thickness and the type of macular edema: diffuse, cystic, or with neuroepithelial detachment at the foveal level due to the presence of subretinal fluid. We correlated the macular ischemia data of OCT‐A with the classical OCT data to see if there is any relationship.

Results

It is verified that all parameters have a higher value in patients who do have macular edema and that in one of the measured characteristics (the diameter of the superficial plexus) this difference is statistically significant. Finally, when observing the values of the effect size, it is verified that there are three parameters (FAZ Plexus superficial, Diameter of superficial plexus superficial and Diameter of deep plexus) where a higher clinical significance is obtained.

Conclusions

There is a positive association between the area and diameter of the ZAF and the presence of macular edema in diabetic patients.
Release of cytokines/myokines by retinal tissue at different times in a mouse model of glaucoma
Authors: Fernández‐Albarral José A. , Ramírez Ana I. , de Hoz Rosa , López‐Gallardo Meritxell , Moya M. , Marco E. , ElenaSalobrar‐García  , MarcelinoAvilés‐Triguero  , Villegas‐Pérez Maria P. , Salazar Juan J. , Ramírez José M. , Ramírez José M.
Published: December 2019

Diverse cytokines released by retinal glial cells (IL‐1β, IL‐4, IL‐6, IL‐10, IL‐17, IFN‐, BDNF, VEGF and Fractalkine) were analyzed in order to determine the changes in the expression, at different times after unilateral laser‐induced ocular hypertension (OHT), both in OHT eyes and their contralateral eyes respect to naïve eyes.

At each of time point after OHT induction (days 1, 3, 5, 7 and 15), 12 OHT retinas, 12 contralateral retinas and 12 naïve retinas (lasered group n = 60, naïve n = 12) from Albino Swiss mice were analyzed. The samples obtained were processed and multiarray kits (MILLIPLEX MAP Mouse Cytokine/Myokine Magnetic Bead Panel) were used to quantify the expression of cytokines.

In OHT eyes, the expression of the following cytokines: BDNF (1, 3, 7 and 15 days), VEGF (1 day), IL‐4 (at all‐time points except day 15), IL‐6 (1, 3 and 5 days), IFN‐ (3, 5 and 15 days), IL‐10 (3 and 5 days), and Fractalkine (1 day) were significant higher than in naïve. In contralateral eyes, the following cytokines: IL‐6 (1, 5 and 7 days), IL‐1β (1 and 3 days), IL‐4 (7 and 15 days), IL‐10 (7 days) and IL‐17 (15 days) showed a significant increase in comparison with naïve

After unilateral laser‐induced ocular hypertension, OHT eyes and contralateral eyes showed changes in the expression of the anti‐ and pro‐inflammatory cytokines associated with inflammatory process, mainly 3 days after OHT induction. These factors, which may be released by activated macroglia and microglia, may exert neuroprotective and neurodegenerative effects.

This work was supported by Ophthalmological Network OFTARED (RD12‐0034/0002 and RD12/0034/0014. Prevención, Detección Precoz y Tratamiento de la Patología Ocular Prevalente Degenerativa y Crónica), the Institute of Health of Carlos III of the Spanish Ministry of Economy; PN I+D+i 2008‐2011; ISCIII, General Subdirection of Networks and Cooperative Research Centers; by the FEDER European program. Grants to J.A. Fernández‐Albarral are currently supported by a Predoctoral Fellowship (FPU) from the Spanish Ministry of Science, Innovation and University.
Role of interferon alpha 2b (IFN‐α2b) in the treatment of conjunctive squamous neoplasia
Authors: Diaz Maria Dolores , Boned Ana , del Buey Maria Angeles , Marco Sara , López Isabel , Karlsruher Gisela , Montes Paula , Ascaso Francisco Javier
Published: December 2019

Purpose

IFN‐α2b has been postulated as an effective treatment to treat ocular surface tumors since the mid‐1990s. It could be used as a neoadjuvant agent, adjuvant therapy if there are positive margins after resection or as a primary agent for small tumors. It causes anti‐angiogenic, anti‐proliferative, cytotoxic and immunomodulatory effects. Consequently, it reduces the number of recurrences with few and mild side effects.

Methods

We present the case of a 77‐year‐old man with history of right eye cataract surgery who was seen in our Ophthalmology Department, due to a new appearance of a conjunctival tumor in the upper and lower temporal sectors, arriving at the bulbar conjunctiva with corneal invasion in the right eye. After performing a biopsy, squamous cell carcinoma with mild dysplasia was diagnosed. Ultrasonography and MRI were requested, ruling out infiltration. Surgical excision and amniotic membrane implantation were decided. Despite starting treatment with mitomycin C (MMC) 4 times a day, he suffered from a temporary recurrence. A second excision was performed 3 months later. This time, treatment with IFN‐α2b was started 4 times a day.

Results

IFN‐α2b is consolidating as a postoperative adjuvant treatment. In our case, it has managed to avoid new recurrences. We observed an asymmetric rise of the intraocular pressure (IOP) which could be associated with IFN‐α2b and need antihypertensive ocular topic treatment.

Conclusion

Nowadays, surgery remains the gold standard in the treatment of these tumors. Nevertheless, the high rate of recurrences and the appearance of different treatments makes search for an optimized treatment of these patients possible and necessary. IFN‐α2b stands out in terms of cost‐effectiveness and must be present among the therapeutic arsenal of any ophthalmologist who faces this carcinoma but it side effects should be studied.
Clinical Experiences in Flash Adaptometry
Authors: Krastel Hermann , Zyganow Marlene , Kaltakji Feras , May Michael , Schlichtenbrede Frank
Published: December 2019

Purpose

To demonstrate that flash adaptometry can easily be applied in clinical routine as extension of the ISCEV Standard Ganzfeld ERG.recording protocol.

Methods

The flash adaptometer has already been presented to the EVER community (2017). To avoid ocular electrode displacement during the 20 min of dark adaptation, stable conditions of recording are now maintained by skin electrodes. The small (5 mm of diameter) active electrode is placed onto the middle of the lower eyelid margin just below the eyelashes. Standard gold cup electrodes on temple and forehead provide reference and grounding. After dark adaptation, sensory thresholds are determined for perception of the 6,7 Hz ganzfeld stimuli and for recognition of a 10° contrast grid. Simultaneously, ERG ganzfeld thresholds are recorded.

Results

Recordings are shown in cases of age‐related macular degeneration, retinitis pigmentosa of dominant inheritance, late onset retino‐choroidal degeneration, congenital stationary night blindness and congenital achromatopsia.

Conclusion

By flash adaptometry, a supplementary functional parameter of sensory and retinal function can be recorded in a clinical setting at small expense in time and no additional patient encumbrance.
Cell‐type specific insights into the pathobiology of advanced diabetic retinopathy using single‐cell transcriptome analysis of the Akimba retina
Authors: Van Hove Inge , Porcu Michaël , De Groef Lies , Hu Tjing‐Tjing , Beets Karen , Van Bergen Tine , Boeckx Bram , Lambrechts Diether , Moons Lieve , Feyen Jean H.M.
Published: December 2019

Purpose

In this study, single‐cell transcriptomics was applied to provide insight into cell‐type specific transcriptional dynamics in the neuronal, glial, vascular and inflammatory compartments of the Akimba retina. Investigation of the molecular characteristics and networks underlying the pathobiology of this diabetic retinopathy mouse model might lead to the identification of new pathophysiological or protective mechanisms.

Methods

Retinas were isolated from 12‐week‐old Akimba (Ins2AkitaVEGF+/‐) and age‐matched wild type (WT) C57BL/6J mice and dissociated by collagenase treatment into single cell suspension. Single‐cell barcoded libraries were generated (10× Genomics) and sequenced on the Illumina HiSeq4000 platform. After data pre‐processing, principal component analysis‐based clustering was performed, and clusters were annotated based on marker genes. In addition, differential expressed genes between Akimba and WT retinal cells were further analyzed for statistically enriched pathways and categorized for biological function using STRING.

Results

Our results showed that neuronal cell death, especially of the rod photoreceptors, is accompanied by an immune response in the Akimba versus WT retina. This is demonstrated by the prominent increase in and activation of resident and invading immune cells and enrichment of e.g. complement, interferon and inflammasome signaling pathways. Transcriptional changes in macroglia point towards their attempt to rescue lost tissue via reactive gliosis, and towards a metabolic shift from glycolysis to oxidative phosphorylation. In addition, the Akimba retina is also characterized by an overall change in ribosome synthesis and translation, oxidative stress responses and metal dyshomeostasis.

Conclusion

Our data indicate substantial shifts in abundance of cell types in the Akimba retina, and cell‐specific changes that may lead to functional uncoupling of neuron‐glia interactions.
Visual outcomes of Descemet Membrane Endothelial Keratoplasty at a Single Surgeon United Kingdom Centre
Authors: Pekacka Aleksandra , Malik Hammad , Garella Manisha , Barsam Allon
Published: December 2019

Purpose

Descemet Membrane Endothelial Keratoplasty (DMEK) is a partial thickness corneal graft which involves replacing a recipient’s Descemet’s membrane and endothelium with healthy tissue. Main advantages include rapid visual recovery, fewer higher order aberrations and low rejection rate. However, DMEK is technically challenging and requires advanced surgical skills. The aim of the audit was to assess visual outcomes of DMEK performed at Luton and Dunstable University Hospital (L&D), United Kingdom.

Methods

Data was collected retrospectively from April 2015 to November 2018. 57 eyes were analysed (31 male, 26 female). Patient demographic data were collected, as well as indication for surgery and pre‐operative visual acuity. Post‐operative follow‐up visits were analysed, including assessment of visual acuity, complications and graft failure and rejection.

Results

Pre‐operative visual acuity (Snellen chart) ranged from worse than 6/60 to 6/6. At an average of 6 months post operatively 87% of patients achieved 6/12 vision or better. At 1 year post procedure 59% of patients achieved 6/6 vision or better. At 2 years follow‐up 63% of patients achieved 6/6 vision or better. The most common DMEK related complications were steroid induced raised IOP (n = 9), partial graft detachment or dislocation (n = 8) and need for re‐bubbling (n = 7). 5 patients were listed for Descemet Stripping Automated Endothelial Keratoplasty (DSAEK).

Conclusions

Most patients undergoing DMEK procedure in L&D Hospital achieve 6/12 vision or better from 6 months onwards. Outcomes at 6 months, 1 year and 2 years are in‐line with the guidelines set by the Royal College of Ophthalmologists and previously published data. These are re‐assuring findings which suggest that more advanced corneal techniques can be carried out at single surgeon sites. Future work should aim to collect long term data on outcomes.
Clinical efficacy of MC2‐03 (ciclosporin eye drop) in treatment of dry eye disease patients with severe keratitis randomized in the NORTHERN LIGHTS phase 2b trial
Authors: Praestegaard Morten , Gomez Frédéric , Teus Miguel A. , Horwath‐Winter Jutta , Heegaard Steffen
Published: December 2019

Purpose

Anti‐inflammatory treatment of moderate‐to‐severe dry eye disease (DED) remains a challenge with a need for eye drops showing better efficacy and tolerability. The effect of MC2‐03, a novel ciclosporin (CsA) eye drop using PAD™ Technology, was investigated in humans.

Methods

The NORTHERN LIGHTS trial is a 6 month phase 2b, multicenter, randomized, controlled, double‐masked trial evaluating MC2‐03 (0.03% and 0.06% CsA) administered once daily in 255 patients with moderate‐to‐severe DED with grade 3 and 4 corneal fluorescein staining (CFS) on the modified Oxford scale. The primary objective of the study was to evaluate safety and efficacy of two doses of MC2‐03 compared to vehicle and lubricant comparator. A total of 108 (42.4%) patients with severe keratitis (CFS 4) at Baseline were randomized.

Results

The proportion of patients with severe keratitis (CFS 4) at Baseline achieving at least 2‐grade improvement in CFS at Month 6 was 63.0% for MC2‐03 0.03%, 41.4% for MC2‐03 0.06% versus 30.8% for both vehicle and lubricant comparator, showing statistical significant improvement for MC2‐03 0.03% compared to vehicle (p = 0.028) and to lubricant (p = 0.028). Further post‐hoc analysis demonstrated that the mean change in CFS from Baseline to Month 6 for MC2‐03 0.03% separated significantly from vehicle (0.8 CFS units, p = 0.012) and lubricant (0.7 CFS units, p = 0.020) with statistical significance already achieved at Month 3. Overall, the trial demonstrated favorable safety of MC2‐03.

Conclusion

A large unmet need exists for treating moderate‐to‐severe DED patients. The NORTHERN LIGHTS study confirms that MC2‐03 0.03% CsA is effective in treating severe keratitis in this patient group
Relationship between retinal thinning, disease duration and disability status in multiple sclerosis patients
Authors: Viladés Elisa , Orduna Elvira , Cordón Beatriz , Perez‐Velilla Javier , José Vicente Maria , Gil‐Arribas Laura , Fernandez‐Tirado Javier , Haro Erika , de Gopegui Erika Ruiz , Jesús Rodrigo‐Sanjuan Maria , Satué Maria , Garcia‐Martin Elena
Published: December 2019

Purpose

To assess changes in the pattern of the neuro‐retina thinning during the evolution of multiple sclerosis (MS).

Method

64 eyes of healthy controls and 89 eyes of patients with MS without previous episode of optic neuritis were included in the study. Measurements were performed using the Posterior Pole Retinal Thickness Map protocol [shows the thickness of the retina throughout the posterior pole (volumetric examination of 30° × 25° OCT]) with the Heidelberg Spectralis optical coherence tomography (OCT) device. We analysed the 8 × 8 grid placed along the fovea symmetrically with the papilla, dividing patients with MS into 5 different groups at intervals of 5 years of disease duration and a group of patients with a few months of diagnosis.

Results

MS patients presented a significant thinning of the retinal nerve fibre layer (RNFL) and the ganglion cell layer (GCL). This thinning is visible and significant even in the first year after symptoms onset in RNFL and GCL. In addition, an inverse relationship between the thickness of these layers and the time of disease evolution was found, existing cells with a moderate‐strong relationship mainly in the GCL and RNFL. In contrast there is negative but poor correlation between retinal thinning of these 2 retinal layers and Expanded Disability Status Scale (EDSS).

Conclusion

Although there is no significant peripapillary damage in the first months of the disease, we can find a significant thinning in the RNFL and GCL around the macula. GCL seems to be the layer that presents a significant thinning earlier than the RNFL and stronger relationship with disease duration. On the other hand, EDSS does not seems to be so influent on retinal thinning than disease duration.
Do patients receiving laser treatment for sight threatening diabetic retinopathy and those under the care of a consultant led multidisciplinary diabetes specialist team have better HbA1c value than those that are not under a diabetes specialist?
Authors: Ahmed Syed , Shahid Syed , Parmar Sita , Kashani Shahram
Published: December 2019

Purpose

To evaluate if patients with sight threatening diabetic retinopathy who undergo laser photocoagulation treatment and are under the care of a consultant‐led specialist diabetes team have a better HbA1c value than those that are not under a specialist diabetes team.

Methods

Retrospective review of all patients who underwent pan laser photocoagulation (PRP) treatment or macular laser therapy between 1st January 2018 and 31st December 2018 were included in the study.

Results

We identified 64 patients who underwent laser treatment for diabetic retinopathy in the 12‐month period, 21 female and 43 male. Of these, 36 patients (56%) had type‐2 diabetes, 12 patients (18%) had type‐1 diabetes and in 16 patients (25%), this was undocumented. In terms of type of laser therapy, 50 (78%) underwent PRP and 14 (22%) underwent macular laser. 33 patients (51%) who underwent laser treatment were under the care of a specialist diabetes team within 1 year of receiving treatment. The average HbA1c value of patients who were under a diabetes specialist was 80.9 mmol/mol (9.6%), versus those who were not under a diabetes specialist was 72.7 mmol/mol (8.8%).

Conclusion

Our study showed that amongst patients who underwent laser treatment for sight threatening diabetic retinopathy, majority underwent pan retinal photocoagulation for proliferative disease rather than macular laser for maculopathy. This observation is expected, as macular laser is less commonly practiced since the advent of anti‐VEGF therapy for diabetic maculopathy. Surprisingly, the HbA1c values on average were better in those who were not under a specialist diabetes team compared to those who were under the care of a specialist. Although this is unexpected, it may be explained by the fact that those under a diabetes team have poorer control of their blood sugars, and/or more advanced diabetes to begin with.
A case of bilateral acute angle closure glaucoma secondary to systemic decongestants
Authors: Jin Hui Goh Eunice , Neelam Kumari , Sangtam Tiakumzuk , Stanley Philip
Published: December 2019

Purpose

To report a case of bilateral acute angle closure attack secondary to an oral decongestant and antihistamine use.

Methods

A case report.

Results

A 42‐year‐old Chinese lady with no past medical or ocular history presented to the Emergency Department with a 2‐day history of headache, vomiting and bilateral eye redness. She had taken pseudoephedrine and chlorpheniramine the previous 5 days for cold symptoms. Best‐corrected visual acuity (BCVA) was 6/24 bilaterally. Her intraocular pressure (IOP) was 37 (right) and 39 (left) mmHg. On slit lamp examination, the corneas were hazy and edematous with mid‐dilated pupils. Gonioscopy revealed closed angles bilaterally. Glaukomflecken was noted on both lenses. A diagnosis of bilateral acute angle closure attack was made. She was immediately given intravenous acetazolamide and topical hypotensive drops (timolol 0.5%, brimonidine 0.1%, prednisolone acetate 1% and pilocarpine 2%) followed by oral acetazolamide and continuation of all the topical drops. 9 hours later, the BCVA had improved to 6/15 (right) and 6/9.5 (left). Her left cornea was clearer but right was still hazy. IOP was 32 (right) and 14 (left) mmHg. B‐scan ultrasound showed no choroidal thickening. Subsequently, a bilateral laser iridoplasty was performed followed by laser iridotomy. Her IOP normalized after the procedures to 8 mmHg in both eyes.

Conclusions

Several systemic medications are known to precipitate angle closure glaucoma. It is important to counsel patients on risks and symptoms before initiating these seemingly benign medications for a common cold.
cGAS‐STING pathway activation in murine retina
Authors: Tang Miao , Pavlou Sofia , Chen Mei , Xu Heping
Published: December 2019

Purpose

The intracellular DNA sensor, cGAS, initiates the host immune response by recognizing pathogen‐ or endogenous‐derived cytoplasmic DNA. After binding to DNA, activated cGAS‐STING pathway induces the transcription of the Type I interferon and other pro‐inflammatory genes. Mitochondrial dysfunction is known to be involved in various retinal degenerative and angiogenic diseases, including age‐related macular degeneration and diabetic retinopathy. As a consequence of mitochondrial stress, cytosolic escape of mitochondrial DNA has been reported to induce cGAS‐STING pathway activation. In this study, we characterized the expression of cGAS‐STING pathway in murine retina.

Methods

The expression of cGAS and STING in murine retina, microglia cells (BV2), primary RPE and B6‐RPE07, primary Müller glial and photoreceptor cells (661W) was examined by RT‐PCR and immunohistochemistry. The cells were transfected with exogenous dsDNA poly(dA:dT) (5ug/mL) for 8 hours. The expression of cGAS, STING, phosphorylated TBK1 (pTBK1) and IRF3 (pIRF3), type‐1 interferon, IL‐6 and TNFa was analysed by RT‐PCR and immunocytochemistry.

Results

Both cGAS and STING were detected in the murine retina, microglia, Müller glial, photoreceptor and RPE cells. Following poly(dA:dT) treatment, the expression of cGAS and pTBK1 was increased in these cells. In addition, intranuclear translocation of pIRF3 was observed in poly(dA:dT)‐treated microglia, RPE, Müller glial and photoreceptor cells. In line with these observations, the mRNA expression of IFNa, IFNb, IL6 and TNFa was significantly increased (p < 0.05) in poly(dA:dT)‐treated cells.

Conclusions

The cGAS‐STING pathway is expressed in many cells within the retina, including microglia, Muller cells, photoreceptor and RPE cells. This pathway may play an important role in retinal innate immunity against endogenous or exogenous cytosolic DNA. Uncontrolled cGAS‐STING pathway may be involved in retinal degenerative diseases.
Synthesis and application of magnetic nanoparticles (MNPs) in siRNA delivery to the retina
Authors: Bassetto Marco , Sen Merve , Gonzalez Blanca Arango , Ueffing Marius , Poulhes Florent , Zelphati Olivier
Published: December 2019

Introduction

Small interfering RNA (siRNA) is an important RNA interference tool that has found significant application in ocular therapy. For this reason, there is a considerable demand of siRNA delivery platforms able to effectively transfect cells within the retina. Up to now several strategies have been investigated for this application such as lipids, nanoparticles and polymers but in all the cases invasive injections are the only administration routes explored. Moreover, a major limitation shared by all these delivery systems is the lack of active targeting toward the posterior segment of the eye that hampers high transfection efficiencies.

Purpose

We aim to synthesize and formulate a new magnetic nanoparticles‐mediated delivery technology that shall allow safe and efficient siRNA delivery to the retina assisted by magnetic targeting.

Methods

(1) Cationic MNPs have been synthesized, characterized, and their ability to form complexes with siRNA has been demonstrated by Zeta Potential. (2) The in vitro MNPs mediated gene silencing have been tested on green fluorescent protein (GFP)‐stably transfected cells (661W & RPE). Also, gene silencing of the endogenous glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) gene has been monitored. (3) Finally, the in vitro toxicity of the formulations has been determined in term of apoptosis, cell proliferation and protein production.

Results

MNPs were able to efficiently complex siRNA while maintain their size and charge. MNPs complexed with siRNA achieved high transfection efficiency and gene silencing of GFP as shown by fluorescence microscopy and flow cytometry. The knock‐down efficiency has been confirmed by targeting GAPDH by immunohistochemistry. Finally, proliferation, apoptosis and total protein content assays demonstrate the full biocompatibility of these gene delivery platforms.

Conclusions

Magnetic nanoparticles are a promising platform for gene therapy in the context of ocular therapy and allow to achieve high transfection efficiencies in retinal cell lines.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie grant agreement No 722717.