bluuebunny/crossref_metadata_2025 huggingface dataset:
Subclinical choroidopathy in systemic lupus erythematosus
Authors: Dias‐Santos Arnaldo , Ferreira Joana , Pinheiro Sofia , Paulo Cunha João , Alves Marta , Luísa Papoila Ana , Francisca Moraes‐Fontes Maria , Proença Rui
Published: December 2019

Purpose

To compare choroidal thickness (CT) between patients with systemic lupus erythematosus (SLE) without ophthalmologic manifestations and a control group. To study the effects in CT of disease duration, disease activity index, medication and systemic comorbidities.

Methods

Cross‐sectional study where spectral‐domain optical coherence tomography with enhanced depth imaging was used to measure CT in 13 locations, subfoveally and at 500‐µm intervals along a horizontal and a vertical section from the fovea. Linear regression models were used.

Results

Sixty‐eight SLE patients and fifty healthy controls were enrolled. CT multivariable results showed a trend toward lower values in SLE patients (12.93–26.73 µm thinner) in all locations, except the inferior quadrants (6.48–10.44 µm thicker). Contrary to the control group, the normal topographic variation in CT between macular quadrants and form the center to the periphery was not observed in the SLE group. Multivariable analysis in SLE group alone revealed a significant negative association with anticoagulants (50.10–56.09 µm thinner) and lupus nephritis (40.79–58.63 µm thinner), and a positive association with secondary Sjogren’s syndrome (73.07 µm thicker). Contrary to controls, SLE patients’ CT did not respond to changes in mean arterial pressure.

Conclusions

CT in SLE appears to be thinner, particularly in the subset of patients with nephritis and taking anticoagulants, suggesting more advanced systemic vascular disease. Choroidal responses to hemodynamic changes may also be altered in SLE.
Comparison between color light‐emitting diode corneal topographer and scheimpflug imager in measuring corneal astigmatism and corneal higher order aberrations
Authors: Hwang Yousook , Kim Da Yeoung , Chung So‐Hyang
Published: December 2019

Purpose

To compare corneal astigmatism magnitude, axis, keratometry, and corneal anterior aberrations between the light emitting diode corneal topography analyzer (Cassini) and Scheimpflug Imager (pentacam).

Methods

This prospective study involved 45 eyes of healthy individuals from Seoul St. Mary’s hospital. For each eye, keratometry, astigmatism and its axis of anterior, posterior and total cornea, higher order aberrations were evaluated with a Scheimpflug Imager (Pentacam HR; Oculus, Wetzlar, Germany) and a color‐LED corneal topographer (Cassini; i‐Optics, The Hague, The Netherlands)

Results

Astigmatism magnitude measured using Cassini® and Pentacam® showed no statistically different but anterior and total astigmatic axis were significantly different between two devices (p < 0.05). Anterior and total mean keratometry were statistically significantly different between two devices (p < 0.05) and J0 and J45 vectors of anterior and total cornea were statistically different (p < 0.05). In addition, Cassini® and Pentacam® showed a discrepancy among total corneal astigmatism, total J0 and J45 vectors. Corneal anterior spherical aberration, vertical and horizontal coma, oblique and horizontal trefoil aberrations were not statistically different between 2 devices.

Conclusions

Astigmatic axis obtained from the two devices based on different principles showed significantly differences. Astigmatism magnitude was not statistically different but showed a discrepancy between two devices.
Intraocular pressure is influenced by ambient temperature in glaucoma patients
Authors: Krebs Johann Ferdinand , Hosari Sami , Lämmer Robert , Mardin Christian , Hohberger Bettina
Published: December 2019

Introduction

Glaucoma is known as multifactorial neurodegenerative disease with intraocular pressure (IOP) as main risk factor. Recent experimental studies showed an impact of corneal temperature on aqueous humour (AH) flow, thus potentially influencing IOP.1 Additionally, temperature was seen to influence fluidity of AH by changing its viscosity.2 As bench to bedside research, the aim of the present study was investigate a potential influence of ambient temperature on IOP in glaucoma patients.

Methods

Sixty‐four eyes of 64 glaucoma patients (34 male, 30 female) of the Erlangen Glaucoma Registry (NCT00494923; ISSN 2191‐5008, CS‐2011) were included between 11/17 and 08/18. All patients underwent a complete ophthalmological examination including Goldmann applanation tonometry (at 12.00 a.m). Daily local temperature (DT) was recorded. Subgroup analysis was done for a winter group (11/17–03/18; mean age: 63.6±12 years; 17 male, 15 female; mean defect 4.93±5.35 dB) and a summer group (04/2018–08/2018; mean age: 70.2±9.9 years; 17 male, 15 female; mean defect 4.68±5.08 dB).

Results

(I) Total IOP of all eyes was 13.61±3.8 mmHg. Subgroup analysis yielded a mean IOP of 14.3±3.6 mmHg in the winter group and 11.7±2.7 mmHg in the summer group. (II) Local DT was 13.96±11.1°C (‐6.8 ‐ +32.9°C) during the year. Winter local DT was measured as 3.28±4.8°C (11/17‐03/18). Summer local DT showed a mean of 24.11±3.7°C (04/18 ‐ 08/18). (III) Mean IOP was observed to be significantly higher in patients of the winter group compared to the summer group (p < 0.001).

Discussion

Experimental ex‐vivo studies suggested that cooler ambient temperatures ‘cools’ AH via corneal surface, decreasing AH fluidity. Thus, AH circulation is lowered with consecutive increase of IOP. Data of the present clinical study bridge these experimental findings, offering ambient temperature as novel influencing factor on IOP in glaucoma patients.

References

Colligris P, Perez de Lara MJ, Colligris B, Pintor J. Ocular Manifestations of Alzheimer’s and Other Neurodegenerative Diseases: The Prospect of the Eye as a Tool for the Early Diagnosis of Alzheimer’s Disease. Journal of ophthalmology 2018;2018:8538573.

Boussommier‐Calleja A, Li G, Wilson A, et al. Physical Factors Affecting Outflow Facility Measurements in Mice. Investigative ophthalmology & visual science 2015;56:8331‐8339.
The role and mechanism of retinal ganglion cell death in glaucomatous injury
Authors: Ali Zara , Mensah Terrance , Felgate Matthew , Watt Robert , Khatib Tasneem Z. , Tribble James R. , Morgan James E. , Martin Keith R. , Osborne Andrew
Published: December 2019

Purpose

Glaucoma refers to a group of diseases characterised by visual field damage and optic neuropathy. In glaucoma, retinal ganglion cell (RGC) death halts the progression of visual information from the eye to the brain, causing permanent visual loss. Due to their crucial role in the pathophysiology of glaucomatous injury, strategies delaying or preventing RGC death are being increasingly recognised as important to incorporate into novel approaches to glaucoma. However, the successful development of such therapies is reliant upon a comprehensive understanding of the mechanisms underlying RGC dysfunction. This study aims to help elucidate this by examining the difference between RGC layer nuclei counts, inner plexiform layer (IPL) thickness, and TrkB signalling in the retina between control and glaucoma human samples.

Methods

Nine healthy and eight glaucomatous retinas were obtained from the Mayo Clinic, US. 2‐3mm explants from peripheral and central regions were probed for p‐TrkB via immunohistochemistry. Six images per retinal section were quantified for TrkB signalling using ImageJ. RGC layer nuclei counts and IPL thickness measurements were taken as evidence of glaucomatous damage.

Results

There was a loss of nuclei in the RGC layer, a decrease in IPL thickness, and loss of p‐TrkB signalling in the peripheral human glaucoma samples compared to controls. These changes correlated with a loss of visual field information. No significant changes were observed in the central retina.

Conclusions

Our findings support the observation that patients lose peripheral vision early in glaucoma. This convincingly supports a picture of RGC death disrupting the transmission of visual information from the peripheral retina in glaucoma patients. Reduced TrkB signalling in glaucoma also demonstrates the importance of this signalling pathway in maintaining RGC survival. Investigating ways to restore, or preserve, TrkB phosphorylation may be beneficial in the treatment of glaucoma.
Effect of intravitreal bevacizumab injection in central serous chorioretinopathy
Authors: Hyeon Song Seok , Kook Baek Seung , Suk Chang Young , Suk Yoon Jung
Published: December 2019

Purpose

To investigate the effect of intravitreal bevacizumab injection on the type of central serous chorioretinopathy.

Methods

We performed a retrospective analysis of 43 patients (43 eyes) who were diagnosed with central serous chorioretinopathy and underwent intravitreal bevacizumab injection from March 2014 to March 2018. The best corrected visual acuity (BCVA) and central macular thickness (CMT) before and 3, 6, 9, and 12 months after injection were compared according to the type of central serous chorioretinopathy. The types of central chorioretinopathy were classified as acute (onest < 6 months), chronic (onest ≥ 6 months), and recurrent group.

Results

43 eyes of 43 patients, 10 eyes of acute group, 21 eyes of chronic group, and 12 eyes of recurrent group. Age, sex, initial BCVA, CMT, duration of follow‐up, and the number of intravitreal bevacizumab injection were not significantly different between the three groups (p > 0.05). The BCVA (logMAR) was not significantly different between the three groups before, 3, 6, 9, and 12 months after the injection. But, at 3, 6, 9, and 12 months after injection, the BCVA of the chronic group tended to be worse than that of the acute group and the recurrent group. The CMT was not significantly different between the three groups before, 3, 6, 9, and 12 months after injection. But, at 12 months, the CMT of the chronic group tended to be larger than that of the acute group and the recurrent group. In each group, a comparison of the initial BCVA and BCVA at 12 months, initial BCVA and final BCVA, and initial CMT and CMT at 12 months showed a significant decrease in the CMT at 12 months compared to the initial CMT in the acute group

(p = 0.005). There was no statistical significance in the chronic group. In the recurrent group, both the BCVA at 12 months (p = 0.007) and final BCVA (p = 0.011) improved significantly compared with the initial BCVA. The CMT was also significantly decreased at 12 months compared to the initial CMT (p = 0.006).

Conclusions

We concluded the effect of intravitreal bevacizumab injection on the improvement of BCVA and CMT in acute and recurrent central serous chorioretinopathy.
Clinical results according to cause of endophthalmitis
Authors: Hyeon Song Seok , Kook Baek Seung , Suk Chang Young , Suk Yoon Jung
Published: December 2019

Purpose

To analysis clinical features according to the cause of endophthalmitis and evaluate the factors associated with final visual acuity.

Methods

We retrospectively reviewed the medical records of 28 patients with endophthalmitis treated from January, 2014 to December, 2018, and analyzed the clinical features of endophthalmitis and the factors associated with final visual acuity.

Results

The total number of subjects was 28 (28 eyes). The mean age was 65.32 ± 14.85 years old, 22 (78.6%) were male and 6 (21.4%) were female. Of the 28 eyes, 6 eyes (21.4%) had endogenous endophthalmitis, 12 eyes (42.9%) had endophthalmitis after trauma, 9 eyes (32.1%) had endophthalmitis after cataract surgery, and 1 eye (3.6%) has endophthalmitis after intravitreal bevacizumab injection. The most common cause was trauma. The mean time to treatment after symptom onset was 0.88 ± 2.62 days and the mean follow‐up period was 14.93 ± 14.22 months. The mean final visual acuity (logMAR) of each cause was 0.63 ± 0.83 for cataract surgery, 1.43 ± 0.73 for endogenous, 1.60 ± 0.44 for trauma, and hand motion for intravitreal bevacizumab injection. In the case of endophthalmitis after cataract surgery, final visual acuity improved significantly compared with initial visual acuity (p = 0.028). According to time from event or symptom to diagnosis, the mean final visual acuity was 1.37 ± 0.65 in 2 days, 1.15 ± 0.96 in 3–7 days, and 1.16 ± 0.91 in 7 days. In cases of less than 2 days, final visual acuity improved significantly compared to initial visual acuity (p=0.037). According to initial visual acuity, the mean final visual was 1.88 ± 0.25 with less than light perception, 1.23 ± 0.64 with hand motion, 1.04 ± 0.95 with finger count, and 0.48 ± 0.57 with above 20/400. The higher the initial visual acuity, the higher the final visual acuity. The better the initial visual acuity, the higher the final visual acuity (p = 0.005, Kruskal–Wallis test).

Conclusion

We concluded that the initial visual acuity and the cause of endophthalmitis are related to the final visual prognosis.
Longitudinal morphological assessment of macular changes in glaucoma
Authors: Mercuri Stefano , Davis Benjamin , Yap Timothy , Cordeiro Maria Francesca , Normando Eduardo Maria
Published: December 2019

Purpose

To investigate the role of longitudinal analysis of macular Optical Coherence Tomography (OCT) scans in identification of glaucoma progression.

Methods

40 eyes of 20 patients diagnosed with glaucoma were retrospectively assessed over a period of 3 years with visits intervals of 4–6 months. Data were acquired at each time point with Posterior Pole (PPole) and Peripapillary RNFL protocols. Following automatic layer segmentation and macular regional subdivision, measurements of total retinal, Retinal Nerve Fiber Layer (RNFL) and Ganglion cell layer (GCL) thickness were recorded. Thickness gradients and linear regression analyses were calculated for each macular region in each eye longitudinally over time using “R” software (https://www.R-project.org). All data are expressed as mean ± SD. p < 0.05 was considered as significant.

Results

Linear regression analysis of each individual region showed that macular morphological analysis detected progression significantly earlier than RNFL peripapillary scan in 90.4% (total retina: 3.8 ± 0.8 visits versus 6 ± 0.9 visits, p <0.0001), 96% (RNFL:

3.7 ± 0.6 visits versus 5.6 ± 0.6 visits, p < 0.0001) and 83% (GCL: 4 ± 0.8 visits versus 5.6 ± 0.7 visits, p < 0.01) of eyes. Interestingly, in 78% of progressing glaucomatous eyes, a supero‐temporal thinning of whole retina, RNFL and GCL could be detected.

Conclusion

In this study we have shown that longitudinal analysis of macular morphology is able to detect and quantify glaucoma progression. Macular thickness changes represent a potential biomarker for glaucoma diagnosis and detection of early disease progression.
Subthreshold laser compared to spironolactone in treatment of chronic central serous retinopathy
Authors: Mercuri Stefano , Corazza Paolo , Khairat Nancy , Younis Saad
Published: December 2019

Purpose

To compare clinical and morphological outcomes of Subthreshold Laser and Spirolonactone in treatment of chronic central serous retinopathy (CSR).

Methods

Patients with chronic CSR (visual symptoms > 6 months) treated either with Subthreshold Laser or Spirolonactone were recruited. Patients data were recorded at four time points: at initiation of treatment, at 1 month, at 3 months and at the last follow up possible. Main outcome measures included best‐corrected visual acuity (BCVA), central macular thickness (CMT), location and height of subretinal fluid (SRF), degree of photoreceptors outer segments (POS) damage, presence of pigmented epithelium detachment (PED), integrity of retinal pigmented epithelium (RPE).

Results

Forty‐seven eyes of 45 patients and 45 eyes of 42 patients were included in the Subthreshold Laser and Spirolonactone groups, respectively. Mean number of sessions of Subthreshold Laser per patient was 1.36 ± 0.5, while mean number of Spirolonactone cycles was 1.66 ± 1.0. In patients undergoing Subthreshold Laser, BCVA did not significantly improve at all timepoints, while patients undergoing Spirolonactone showed increased visual acuity in the long term (p = 0.011), but not at 1 month and at 3 months. Both Subthreshold Laser and Spirolonactone significantly improved CMT, CFT, SRF at all timepoints (all p < 0.05). Spirolonactone allowed a significantly higher CMT and SRF decrease compared to Subthreshold Laser at 3 months (p = 0.048 and 0.036, respectively). Spirolonactone side effects occured in 5 patients (11%), while none of patients in the Subthreshold Laser group developed RPE atrophy.

Conclusions

Treatments with Subthreshold Laser and Spirolonactone are effective in fluid reduction at every time point in chronic CSR, while not giving substantial improvement in visual acuity at 1 month and at 3 months. Spirolonactone allows a significantly higher visual recovery in the long term, while allowing a significantly higher fluid reabsorption at 3 months compared to Subthreshold Laser.
Short‐term results of clinical monitoring of biosimilar infliximab in non‐infectious uveitis
Authors: Mortelé Marie , Mortelé Augustijn , Vervaeke Steven , Deschoenmakere Gert , De Schryver Ilse
Published: December 2019

Purpose

To observe the efficacy, safety and immunogenicity of biosimilar infliximab (CT‐P13) in patients with refractory non‐infectious uveitis (NIU).

Methods

Retrospective observational study. Indication for treatment was active uveitis unresponsive to classical immunosuppressants. Clinical data were retrospectively analyzed at baseline and 3 months of treatment. The main outcome measures were uveitis activity, adverse effects and serum biosimilar infliximab trough concentrations as well as anti‐infliximab antibodies (ATI).

Results

Nine patients received biosimilar IFX after failing classical immunosuppressive treatment. Mean age was 53 years. The most common diagnosis was Birdshot (n = 4), followed by sarcoidosis (n =3 ), Behcet (n = 1), and Sympathetic Ophthalmia (n = 1). The duration of treatment ranged from 18 to 192 weeks. Five patients without active disease and one patient with activity had IFX levels >9 μg/mL. Two patients with active disease and 1 patient in remission had undetectable levels of IFX. Two patients with undetectable levels of IFX had positive anti‐infliximab antibodies (ATI) levels; both patients showed activity. The other patient with undetectable levels of IFX had no ATI and was in remission. None of the patients with IFX levels >9 μg/mL had positive ATI levels. One patient dropped out of treatment due to infusion‐related skin eruptions.

Conclusion

Biosimilars are pharmacologically highly similar to an approved biological pharmaceutical ‘reference’ product, but are not exact copies. Even if limited to a small group, this study provides evidence that low biosimilar IFX trough levels associate with increased antibodies in most, but not in all cases.The clinical use of measuring biosimilar infliximab (IFX) trough levels and antibodies against IFX (ATIs) remains unclear.
In Vivo anterior Optic Nerve Head changes as a function of Visual Field loss in Glaucoma
Authors: Lee Bartlett Ryan , Frost Bethany E , White Nick , Fergusson James R , Morgan James E , V North Rachel , Albon Julie
Published: December 2019

Purpose

To correlate regional measures of prelamina (preL) depth and thickness, anterior lamina cribrosa (LC) depth and nerve fibre layer (NFL) thicknesses with change in visual field sensitivity in primary open angle glaucoma, using enhanced depth imaging optical coherence tomography (OCT).

Methods

Three‐dimensional image datasets were acquired as 20° scans centred on the optic nerve head (ONH) of glaucoma (n=111) and control (n=39) eyes, using a custom built OCT at 1040nm (spectral bandwidth 70nm). ONH measurements of regional (superior [S], inferior [I], nasal [N], temporal [T], and central [C]) preL and anterior LC depth were performed using Bruch’s membrane opening as a reference plane. PreL thickness was calculated from these surface measures. Border (above BMO) and peripapillary (pp) NFL were also measured. Intraclass correlation coefficients (ICC) were used to determine intra‐session repeatability.

Results

PreL depth (S: r=0.339, I: r=0.363, and N: r=0.317; p<0.001, T: r=0.219, p=0.007, central: r=0.202, p=0.013) and anterior LC depth (S: r=0.232, p=0.006, I: r=0.229, p=0.006, N: r=0.246, p=0.009, T: r=0.169, p=0.04, central: r=0.226, p=0.006) significantly increased with increasing VF loss in all ONH regions. PreL thickness significantly decreased with increasing VF loss in all ONH regions, (S: r=‐0.295 and I: r=‐0.346; p<0.001, N: r=‐0.218, p=0.026, temporal: r=‐0.177, p=0.031), except for the centre (r=‐0.106, p=0.199). ICCs >0.9 were calculated for all ONH measures and intra‐session differences in the ONH parameters were not identified within triplicate image datasets (p>0.05). BNFL and ppNFL thicknesses significantly decreased with VF loss (p<0.001).

Conclusions

Significant correlations were found between preL depth and thickness, and anterior LC depth with VF function, indicating that these quantitative (and repeatable) measures are useful in monitoring glaucomatous optic neuropathy.
Integrated pilot medical study on 40 patients affected by open angle glaucoma undergoing topical therapy with additional osteopathic manipulation
Authors: Paoli Daniela , Brusini Paolo , Michelin Leonardo , Vassallo Fabizio , Ciullo Luigi , Torelli Lucio
Published: December 2019

Purpose

Malfunction of the lymphatic or glymphatic system recently shown in the brain, seems to play an important role in central neurodegenerative pathologies through a build‐up of neurotoxins. Recent studies have shown functional links between aqueous humour and cerebrospinal fluid via the glymphatic system, offering new perspectives and unifying theories on the vascular, biomechanical and biochemical causes of chronic and open‐angle glaucoma (POAG). The aim of this randomized pilot study is to compare the variations in intraocular pressure between 20 cases of compensated POAG under pharmacological therapy and 20 glaucoma patients undergoing osteopathic treatment, hypothesizing that this manipulation can influence intraocular pressure.

Materials and Methods

The 40 patients under study, all covered by the Helsinki convention, were randomly divided into 2 groups (treated group or TG and control group or CG). The 40 patients were chosen from compensated glaucoma sufferers, who required neither changes in therapy nor operations which would affect their eye pressure which was measured both before and after manipulative osteopathic treatment scheduled into 4 sessions at intervals of 7.3 and 150 days, then compared with the control group (20 patients) who were undergoing pharmacological treatment only.

Results

The average IOP in the TG was compared with the CG throughout the entire treatment cycle showing a statistically inconclusive reduction in the right eye RE P‐value (0.0561), while for the left eye a significant effect was shown LE (0.0073). The difference between the reduction in IOP between TG and CG was observable 10 months after the first session or rather 5 months after the last, and demonstrable during a check‐up 13 months after the beginning of the study, or rather 8 months in absence of treatment with a highly significant statistical p‐value (0.000434).

Conclusions

This study has shown that manipulative osteopathic treatment can affect intraocular pressure after each session and that the pressure is significantly lower even months after the last treatment session.
Assessment of intraocular pressure with an artificial model eye mimicking human eye
Authors: Lee Seung Hyen , Cho Han Saem , Jeoung Sae Chae
Published: December 2019

Purpose

Given that clinical significance of intraocular pressure (IOP), accurate IOP measurements are crucial. However, measurement of IOP is affected by corneal properties such as thickness, curvature, and biomechanical properties. To derive the quantitative relationship between corneal variables and IOP, it is valuable to create a theoretical model that represents these various properties of the cornea. We have constructed optically transparent artificial eye phantoms, which have closely similar to a human eye. The purpose of this study is to evaluate the clinical applicability of artificial eye by understanding and quantifying the IOP measurement.

Method

The artificial model eye has made of polydimethylsiloxane (PDMS) and its inside is filled with glycerol solution. We developed three different shapes of model eye to reflect the variation in corneal diameter and radius of curvature. Corneal properties (i.e., elasticity) were varied according to the formulation of PDMS (Young’s modulus: 1.7 MPa, 0.7 Mpa, and 0.4 MPa) and corneal thickness was differed by varying the concentration of ethylene glycol. The effect of each variable on the measurement of IOP was examined quantitatively using Goldmann applanation tonometry.

Results

The IOP of the model eye showed significant positive correlation with corneal thickness in all shapes of model eye (all p < 0.001). The range of the IOP changed according to Young’s modulus of model eye. (12–80 mmHg, 1–80 mmHg, and 1–32 mmHg in model eyes with 1.7 MPa, 0.7 MPa, and 0.4 MPa, respectively). Relationship between the IOP and thickness differed depending on the Young’s modulus of the model eye.

Conclusions

The IOP of the developed artificial eyeball was successfully measured by Goldmann applanation tonometer in a similar manner to a real human eye. This finding suggests that the artificial model eye may have a value as an independent, reproducible sample that allows comparison of tonometers.
The HuR/ELAVL1 expression is altered in Nrf2‐deficient contexts
Authors: Amadio Marialaura , D’Angelo Irene , Govoni Stefano , Felszeghy Szabolcs , Kaarniranta Kai
Published: December 2019

Purpose

Oxidative stress, inflammation, protein aggregation, are major features of Age‐related Macular Degeneration (AMD). A primary system used by the RPE to neutralize oxidative stress and maintain cellular homeostasis is the transcription nuclear factor E2‐related factor 2 (Nrf2) pathway, whose impairment in AMD is documented. Many Nrf2 targets with a role in AMD are also regulated at post‐transcriptional level by the RNA‐binding protein HuR/ELAVL1. However, the role of HuR and post‐transcriptional control of gene expression in AMD is largely unexplored. We studied the pattern of HuR expression in vitro and in vivo contexts characterized by Nrf2 impairment, as well as in AMD human specimens.

Methods

HuR protein pattern was evaluated by Western blot and immunostaining. Wild type (WT) and Nrf2‐deficient ARPE‐19 cells were used for in vitro study. Retinas from mice deficient in either Nrf‐2 (Nrf‐2 single knockout, sKO), or both Nrf‐2 and PGC‐1α (Nrf‐2/PGC‐1α double knockout, dKO) at one year of age, as well as retinas from age‐matched WT controls, were used for in vivo study. Retinas from human AMD and control subjects were also analysed for HuR expression.

Results

Nrf2‐deficient ARPE‐19 cells show increased HuR levels. Retina from sKO, and especially dKO mice, present an altered HuR expression pattern, mainly featured by higher HuR levels in RPE in comparison to WT animals. Changes in HuR immunostaining were also evident in other retinal layers, such as RGL. Immunohistochemistry performed on a limited number of human retinal specimens suggests altered HuR content in RPE.

Conclusion

HuR expression pattern dramatically changes in Nrf2‐deficient contexts, especially in those featured by elevated oxidative stress, suggesting that a cross‐talk between Nrf2 and HuR pathways exists. These findings represent a step forward a better understanding of the modification of the post‐transcriptional factors in AMD, and suggest that HuR may be relevant in AMD pathophysiology.
Ocular manifestations of testicular lymphoma
Authors: Hopkins Abigail , Airody Archana , Gale Richard
Published: December 2019

Purposes

The testes, brain and eye are considered immune‐privileged sites in which specific cell properties allow certain malignant cells to escape immune system destruction. Rarely such sites may develop B‐cell lymphoma. Testicular lymphoma is a rare disease, most common in elderly male patients, few clinical reports document the association between primary testicular lymphoma and eye disease.

Methods

We report a case of a 75 year old male patient who presented with signs and symptoms which mimicked primary intraocular lymphoma. Given this suspicion, the patient was referred to an ocular oncology unit where a chorioretinal biopsy was taken revealing inflammatory cells with no evidence of malignancy.

Results

A number of months later, the patient re‐presented with deteriorating ocular symptoms, a plan was made for vitrectomy with re‐biospy. At a similar time, the patient presented to his GP with a testicular swelling, imaging revealed a right testicular mass from which biopsies were taken. Histology confirmed diffuse large B cell lymphoma of the testicle, and subsequently the patient was found to have intracerebral disease. The patient unfortunately passed away before further ocular investigation or biopsy.

Conclusion

The presence of vitritis and retinal lesions suggestive of lymphoma in an elderly male patient should prompt investigation of the testes in addition to CNS. A high suspicion for intraocular lymphoma must be maintained with continued close follow up, as early symptoms may be non‐specific and initial vitreous biopsy negative for malignant cells.
Structural Pathology after Retinal Detachment Repair on MultiColor Imaging
Authors: Thomseth Vilde , Engelsvold David , Forsaa Vegard
Published: December 2019

Purpose

To detect and describe features of structural retinal pathology after successful macula‐off reghmatogenous retinal detachment (RRD) repair using MultiColor (MC) scanning laser ophthalmoscopy.

Methods

A prospective study of 30 eyes after recent RRD repair. MC images were evaluated for the presence of RRD related pathology. Detection rates were calculated using swept‐source optical coherence tomography (SS‐OCT) as comparative reference.

Results

The following RRD related lesions were identified: Retinal striae, intraretinal cysts, retinal detachment line, ellipsoid zone disruption (EZD), foveal ellipsoid zone rosette (FEZR), outer retinal fold (ORF), subretinal fluid layer and subretinal fluid blebs. Features of pathology were similar in appearance on MC as compared to enface OCT. Detection rates provided with 95% CI were as follows: retinal striae: 1.00 (0.59–1.0), intraretinal cysts: 0.60 (0.15–0.95), retinal detachment line: 0.84 (0.60–0.97), EZD 0.75 (0.59–0.92), FEZD: 0.73 (0.39–0.94), ORF: 0.86 (0.30‐0.93), subretinal fluid layer: 0.50 (0.12–0.88) and subretinal fluid blebs: 0.70 (0.35–0.93).

Conclusion

MC imaging is sensitive to detect changes in inner and outer retinal architecture after recent retinal detachment repair, and may become a valuable supplement to OCT in yielding information on the photoreceptor integrity following reattachment surgery. The formation of FEZR is not described earlier.
Individuals prevalence affected by myopia in the riverside population of Santarém, Pará, compared to the urban population of Campinas, São Paulo
Authors: Raphaelli Caramel Lais , Scremin Czezacki Alexandre , Albertini Reis Bruna , Oncala Simão Giovanna , Olavarria Gustavo de Campos , Ferreira Greco Henrique , Carinhani Bragheto Isabella , Soares Ricioli Isabella , Anibale Rodrigues Junior José , da Cunha Gobbo Luísa , Benedicto de Souza Marianne , Albuquerque Beckedorff Otto , Giffoni Braga Mont'Alvão Vanessa , José Delfraro Carmo Thiago , Abreu Minussi Luíza , Barbosa Abreu Elvira
Published: December 2019

Purpose

Mensure the prevalence of myopia between 5–14 years and the use of technology between urban and rural populations.

Methods

A prospective, observational, analytical, cross‐sectional, ecological study based on the review of 225 medical records and questionnaires applied in the voluntary project Barco de Saúde São Leopoldo Mandic, in Santarém and in the Penido Burnier Institute, in Campinas. The questionnaire measured the variables: age, sex, age at onset of exposure to technology, exposure time, type of technology and reason for use. Refractometric data were collected from the same autorefractive equipment in the two city to minimize divergences.

Results

Of the 225 patients analyzed, 14.66% are myopic, 27.27% from Santarém and 72.73% from Campinas. It was seen that 78.89% of patients in Pará did not use technology or only used television, in Campinas only 21.11% had this kind of contact. In Campinas there is greater use associated of cell phones, television, computer and tablets, besides the time of technology use in Pará to be between 0 to 3 hours while in Campinas it takes more than 3 hours.

Conclusion

The myopia has its prevalence increasing significantly. It is a disorder with great social impact and eye health. The fast growth of its prevalence has suggested the involvement of environmental factors, such as the extensive use of near vision and poor exposure in outdoor settings. The study evidenced the relevant contribution of the environment.
Unilateral optic nerve axotomy in pigmented mice causes RGCs loss in the contralateral uninjured retina that is prevented by microglial inhibition
Authors: Ruiz Fernando Lucas , Galindo‐Romero Caridad , Rodríguez‐Ramirez Kristy Tatiana , Vidal‐Sanz Manuel , Agudo‐Barriuso Marta
Published: December 2019

Purpose

Unilateral optic nerve crush (ONC) causes in adult mice microglial activation and phagocytosis in contralateral un‐injured retinas [1]. Minocycline is a tetracycline antibiotic that penetrates the central nervous system and inhibits microglial activation. The purpose is to evaluate if an unilateral axotomy (ONC) causes RGC loss in the contralateral retina, and to study if this death is modulated by microglial inhibition with minocycline.

Methods

The left optic nerve of adult male C57Bl/6 mice was crushed at 2 mm from the optic disk. Animals were treated daily by an intraperitoneal injection of minocycline. Both retinas were analyzed 3, 9 or 90 days after the lesion. Controls were retinas from intact animals, and ONC matched groups treated with vehicle. mRNA levels of Casp3, Pou4f1, Rbpms, Sncg were assessed by qPCR. For anatomical analyses retinas were dissected and immunolabelled for Brn3a and Iba1. The total number of RGCs was automatically quantified and their topography assessed by neighbour maps.

Results

In the injured retinas, the loss of RGCs is first significant at day 3, and proceeds up to 90 days when only 1.5% of the original population survives. In the contralateral retinas, there is a significant loss of 15% of the RGCs at day 9 post‐lesion that does not proceed further, at least up to 90 days. Casp3 mRNA is up‐regulated at 3 and 9 days post‐ONC in the injured retinas, and at 3 days in their contralateral ones. The expression of RGC markers decreases over time in the injured retinas, while in their contralateral ones is transiently down‐regulated at 3 days. Minocycline treatment does not rescue RGCs in the injured retinas, but prevents RGC death in their contralateral ones.

Conclusions

In adult pigmented mice, ONC induces RGC loss in the contralateral uninjured retina that may be prevented with systemic minocycline treatment.

Reference

Galindo‐Romero et al., 2013.
Retinal vessel diameters and systemic antioxidant capacity during hypoxia in patients with normal‐tension glaucoma and individuals with ocular hypertension
Authors: Langbøl Mia , Baskaran Thisayini , Tiedemann Daniel , Saruhanian Sarkis , Katrine Toft‐Kehler Anne , Koch Jensen Peter , Skov Jensen Peter , Vidiendal Olsen Niels , Vohra Rupali , Kolko Miriam
Published: December 2019

Purpose

Autoregulation is essential for a constant circulation of O2. The apparent dissimilarity of vulnerability towards increased intraocular pressure in patients with normal‐tension glaucoma (NTGs) and individuals with ocular hypertension (OHTs) has been linked to disturbed autoregulation. The retina is particularly O2‐dependent and susceptible towards oxidative stress. The purpose was to evaluate the impact of a fluctuating O2 level on retinal vessel diameters and plasma levels of vasoregulators, nitric oxide (NO) and endothelin‐1 (ET‐1), and total antioxidant capacity (TAC) in strictly characterized NTGs, OHTs and age‐matched controls.

Methods

NTGs (n = 10–16), OHTs (n = 9–10) and controls (n = 9–14) were exposed to 2 h of hypoxia followed by 30 min of normoxia. Fundus pictures and blood samples were taken before hypoxia (“baseline”), during hypoxia (“hypoxia”) and after hypoxia (“recovery”). NO, ET‐1 and TAC was measured in plasma. Retinal arterial and vein diameters were measured with MATLAB.

Results

Retinal arteries dilated in NTGs and OHTs during hypoxia, while controls constricted. No significant changes were seen in retinal veins. During hypoxia controls and NTGs increased plasma levels of ET‐1 and NTGs sustained a high level in recovery. OHTs did not regulate ET‐1 but maintained a lower level compared to NTGs during hypoxia and recovery. No significant differences were seen in NO. OHTs had a higher TAC compared to NTGs and controls throughout the experiment.

Conclusions

The present study suggests a link between NTG and dysfunctional autoregulation. ET‐1 increase in controls and NTGs during hypoxia. As a vasoconstrictor, a vascular constriction is expected as evident in controls. The observed dilation in NTGs therefore might indicate that molecular mechanisms for vasoregulation are abolished. Surprisingly, OHTs present a similar pattern of autoregulation to NTGs but there is a prominent difference in the TAC. The higher level of TAC in OHTs compared to NTGs and controls indicates that the antioxidant defence might be important in providing resistance towards glaucomatous neurodegeneration.
Characterization and tissue localization of ocular carboxylesterases in multiple species
Authors: Hammid Anam , Vellonen Kati‐Sisko , Ruponen Marika , Urtti Arto , Honkakoski Paavo
Published: December 2019

Introduction

Ocular ADME (absorption, distribution, metabolism & elimination) is gaining interest due to rapidly growing incidence of eye diseases and the need of new therapeutic applications. The information regarding drug‐metabolising enzymes (DME) in different ocular tissues is scattered. In addition, animal models may not be predictive of the human situation due to species differences.

Aim

of the study

We sought to obtain quantitative and functional data of ocular carboxylesterases in multiple species to help comparisons between preclinical animal models and humans.

Methods

Esterase activity assays were optimized using established human‐specific substrates.

Quantitative proteomics was done using specific marker peptides to quantify the selected esterases in ocular tissues of different species (porcine, rabbit and human).

Finally, the functional and quantification data was compared between tissues and species.

Main findings

The rabbit ocular tissues had about 3‐fold higher hydrolysis rates for the generic esterase substrate, p‐nitrophenyl acetate, than the pig tissues. Carboxylesterase 1‐mediated activity (D‐luciferin methyl ester as substrate) in pig ocular tissues were low as compared to rabbit. Moreover, carboxylesterase 2‐mediated activities (fluorescein diacetate as substrate) varied over a 5‐ to 20‐fold range among seven ocular tissues (conjunctiva, cornea, aqueous humor, vitreous, retina, RPE and choroid) in the pig and rabbit, respectively. On average, corneal and choroidal tissues showed high expression and functional activity of carboxylesterase isoforms while retinal pigment epithelium and aqueous humor showed the least activity. More detailed enzymatic and proteomic data will be presented at the poster.

Conclusion

This study provides new insight in ocular esterase expression and esterase‐mediated drug metabolism in multiple species.
Protective effect of lipidure on ocular surface and soft contact lens against desiccation damage
Authors: Cristaldi Martina , Rusciano Dario , Olivieri Melania , Pezzino Salvatore , Lupo Gabriella , Daniela Anfuso Carmelina
Published: December 2019

Purpose

The insertion of a contact lens (CL) disturbs the homeostasis of the tear film, favouring its evaporation and producing friction between the lens and the eyelids and the lens and the ocular surface. These events may induce or aggravate a pre‐existing condition of eye dryness. Lipidure is a biocompatible polymer of 2‐methacryloyloxi‐ethyl‐phosphorylcholine, showing a structure similar to the phosphatidylcholine polar bases; it is endowed with excellent antifouling and moisture retaining abilities. Aim of this study has been to address the protective effects of lipidure, with or without either hyaluronic acid (HA) or hydroxyl‐propyl‐methyl‐cellulose (HPMC), on desiccation of Statens Seruminstitut Rabbit Cornea (SIRC) cells and explanted porcine corneas. Moreover, the ability of lipidure to protect soft CL from desiccation damage and loss of transparency has also been evaluated.

Methods

The protective effect of lipidure was evaluated measuring viability on SIRC cells and explanted porcine corneas leaving them dried at 37°C, 5%CO2 and 95% humidity for 1 h. The ability of lipidure to protect soft CL from desiccation damage and loss of transparency has also been evaluated leaving them air‐dried at 26°C and 46% humidity.

Results

The protective effect of 0.1% lipidure±HA (0.15%) or HPMC (0.3%), was compared to trehalose (3%), a sugar known in nature to protect cells from dessiccation damage. Results obtained indicate that lipidure either alone or in association with HA or HPMC is able to improve corneal epithelial cells survival under desiccation conditions, both in vitro and ex vivo, similar or even better than threalose alone. Moreover, lipidure in association with HPMC can better preserve morphology and transparency of CL from dehydration.

Conclusions

In conclusion, these studies support the use of lipidure both in artificial eye drops to protect the ocular surface form dryness, and as wetting agents for CL improve their tolerance over the eye surface.
Familial aniridia spectrum in four families of Czech origin with PAX6 mutations
Authors: Moravikova Jana , Dudakova Lubica , Kozmik Zbynek , Skalicka Pavlina , Liskova Petra
Published: December 2019

Purpose

To identify disease‐causing mutations in four families with aniridia spectrum of Czech origin, to describe the associated phenotypes and to perform functional assessment of mutations located in canonical splice sites.

Methods

After complex ophthalmic examination of all available family members, DNA extraction from blood or saliva samples was performed. All coding regions of PAX6 gene were Sanger sequenced. In two cases of mutations which could potentially affect splicing of pre‐mRNA functional reassessment was accomplished using Exontrap vector. In one family paternity testing using a standard set of markers was performed.

Results

In total 13 affected individuals were examined. Except for common finding in aniridia, one individual had partial aniridia in the right eye and iris hypoplasia in the left eye, had bilateral ptosis, keratopathy with marked fibrovascular pannus, anterior polar cataracts, foveal hypoplasia, hepatopathy and trombocytopenia of unclear etiology. His affected daughter showed classical aniridia with total absence of iris and foveal hypoplasia in both eyes. Another individual had mild unilateral ptosis and anterior and posterior subcapsular cataracts. Bilateral microcornea, partial aniridia, surgically removed congenital cataracts and large posterior segment coloboma were present in another patient. In four probands, four different PAX6 mutations were identified, one mutation was novel (c.1183+1G>T). Two of detected variants were proven to affect pre‐mRNA splicing by skipping of adjutant exon sequences from mature mRNA.

Conclusion

Loss of visual functions in anterior segment dysgenesis disorders is often very severe, therefore establishing molecular diagnosis highly impacts patient management, enabling prenatal and preimplantation diagnostics. Our study enlarges the spectrum of known PAX6 mutations and confirms that anirida spectrum may also encompass combination of congenital ptosis, severe keratopathy and anterior polar cataracts. Vector Exontrap has been shown as an effective system for the evaluation of variants in canonical splicing sites.

Funding

Supported by SVV 260367/2017 and GAUK 82318‐2018.
In situ forming hydrogel for sustained intraocular drug delivery
Authors: Ilochonwu Blessing C. , Mihajlovic Marko , Tang Miao , Chen Mei , Hennink Wim E. , Vermonden Tina
Published: December 2019

Purpose

Delivery of therapeutic proteins to the posterior segment of the eye faces significant challenges because of frequent intraocular injections, related adverse effects and high treatment costs. This research project aims to design in situ forming hydrogels, which can be easily injected in the vitreous cavity using a small needle. After injection, the polymeric solution undergoes a phase transition to form a cross‐linked hydrogel at the site of administration, entrapping bioactives, which will be released over a prolonged period. In this study, Hyaluronic acid‐modified with furan moieties (HAFU) was successfully crosslinked with four arm‐PEG10K‐maleimide (4APM) yielding stable hydrogels. The potential use of this system for ocular applications was shown by testing the injectability, sustained release of a therapeutic protein and cytocompatibility to retinal cells.

Methods & Results

HAFU‐4APM hydrogels were prepared by mixing an aqueous solution of HAFU and 4APM at physiological conditions to obtain transparent hydrogels. Rheological analysis showed rapid hydrogel network formation at 37°C. The gelation time and final hydrogel stiffness are strongly dependent on polymer concentration. Hydrogel solutions could be injected to the vitreous body of a porcine eye through a 29G needle. Swelling and degradation analysis showed that the hydrogel system is degradable at physiological conditions. The hydrogels showed no toxicity to retinal cells at the used concentrations. HAFU‐4APM hydrogels could sustain the delivery of bevacizumab for 71 days.

Conclusion

Injectable in situ forming hydrogels have been prepared for the sustained retinal delivery of bevacizumab. The formulation has potential for the treatment of age‐related macular degeneration and diabetic retinopathy.

Acknowledgements

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.