bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of sustained‐release bimatoprost implant (Bimatoprost SR) on visual field mean deviation in glaucoma patients in a phase 1/2 clinical trial
Authors: Stalmans Ingeborg , Bejanian Marina , Goodkin Margot , Zhang Jane , Wang Kevin , Rivas Marcos , Robinson Michael , Rhee Douglas J.
Published: December 2019

Purpose

Bimatoprost SR (BimSR), a biodegradable intracameral (IC) implant that slowly releases bimatoprost to lower intraocular pressure (IOP), is in Phase III development for glaucoma treatment. The effect of BimSR treatment on the VF (visual field) MD (mean difference) in glaucoma patients was evaluated in a Phase 1/2 clinical trial.

Methods

Phase 1/2, prospective, 24‐month, dose‐ranging, paired‐eye trial in 75 open‐angle glaucoma patients with required baseline study eye VF loss (per protocol, MD <−1 and >−17 dB). BimSR (6, 10, 15, or 20 μg) was administered IC in the study eye; the fellow eye received topical bimatoprost 0.03% QD (bim). Rescue topical IOP‐lowering medication or a single repeat treatment with implant was allowed. The primary efficacy measure was IOP. Humphrey perimetry 24‐2 full threshold or SITA standard VF testing was done every 6 months. Results are presented for the intent‐to‐treat population and the subgroup treated with the dose strengths of BimSR that are continuing in development (10 and 15 μg).

Results

Mean IOP was reduced by all BimSR dose strengths. IOP was controlled without rescue or retreatment in 68%, 40%, and 28% of BimSR‐treated eyes up to 6, 12, and 24 months, respectively. Month 24 mean (SD) change in MD from baseline was +0.20 (3.16) dB in all BimSR‐treated eyes (n=59), −0.35 (3.04) dB in all topical bim‐treated eyes (n=59), and +0.53 (3.07) dB in BimSR 10‐ and 15‐μg–treated eyes (n=33). Among eyes with no rescue, mean (SD) month 24 change in MD from baseline was +0.71 (3.17) dB in all BimSR‐treated eyes (n=25) and −0.15 (3.03) dB in all topical bim‐treated eyes (n=55).

Conclusions

These results warrant further investigation to assess VF stability using sustained delivery medications compared to topical therapy.
Short and long term effects of NMDA‐induced retinal excitotoxicity on melanopsin and non‐melanopsin containing retinal ganglion cells
Authors: Vidal‐Villegas Beatriz , Di Pierdomenico Johnny , Antonio Miralles de Imperial‐Ollero Juan , Manuel Bernal‐Garro Jose , Paz Villegas‐Pérez María , Vidal‐Sanz Manuel
Published: December 2019

Purpose

To study short and long term responses of the population of RGCs expressing Brn3a (Brn3a+RGCs) and the population of intrinsically photosensitive RGCs expressing melanopsin (m+RGCs) to excitotoxicity induced by intravitreal injection of N‐methyl‐D‐Aspartate (NMDA).

Methods

In adult albino Sprague Dawley rats, the left eye received an intraocular injection of 100nM NMDA and the retinas were analyzed 3 (n=9), 7 (n=6), 14 (n=10) days (d) or 15 (n=23) months (m) later. Spectral Domain Optical Coherence Tomography (SD‐OCT; Spectralis, Heidelberg) was used to image and analyze retinal thickness longitudinally in vivo at short (3 m; n=18) and long (15 m; n=18) survival intervals. Ex vivo, retinal whole mounts were immunodetected with antibodies against Brn3a and melanopsin and the numbers of surviving Brn3a+RGCs and of m+RGCs were automatically counted and represented using isodensity or neighbour maps.

Results

Intraocular injection of 100nM NMDA causes a massive loss of Brn3a+RGCs; at 3 and 14 days Brn3a+RGCs numbers diminished to 50% and 25%respectively, but there was no further loss up to 15 months. However, m+RGCs showed 3 d after injection a transient downregulation of melanopsin that recovered shortly and by 14 d and at the end of the study (15 m) the numbers of m+RGCs were comparable to their contralateral fellow eyes. SD‐OCT examination showed important reductions of the total and inner retinal thicknesses at 3 m that progressed further up to 15 m.

Conclusion

The population of Brn3a+RGCs is quite sensitive to NMDA‐induced excitotoxicity that causes rapidly the loss of approximately 75% of these neurons. In contrast, m+RGCs appear fully resistant to NMDA‐induced excitotoxicity and show only a downregulation of melanopsin expression during the first two weeks. SD‐OCT can be used to assess retinal toxicity revealed by important reductions in total and inner retinal thickness at 3 m progressing up to 15 m.
7,8‐Dihydroxyflavone protects axotomy‐induced retinal ganglion cell loss in adult albino rats
Authors: Vidal‐Villegas Beatriz , Di Pierdomenico Johnny , Salinas‐Navarro Manuel , Manuel Bernal‐Garro Jose , Agudo‐Barriuso Marta , Paz Villegas‐Pérez María , Martínez de la Casa Jose M. , García‐Feijoo Julián , Vidal‐Sanz Manuel
Published: December 2019

Purpose

The substance 7,8‐dihydroxyflavone (DHF) is a potent agonist of the tropomyosin‐related kinase B (TrkB) receptor with a small molecular weight (254 Da) that crosses the blood brain barrier. We analyse the neuroprotective effects of systemically administered DHF on the survival of adult rat axotomized retinal ganglion cells (RGC) expressing Brn3a (Brn3a+RGCs).

Methods

In adult albino rats, the left optic nerve was intraorbitally transected (IONT). Rats were assigned to different groups that received daily intraperitoneal injections of saline (n=16) or DHF at different doses (1 mg/kg, n = 4; 2 mg/kg, n = 6; 4 mg/kg, n = 6; 5 mg/kg, n = 12; 10 mg/kg, n = 6; 25 mg/kg n = 6). Animals were analyzed 7 days after IONT, both retinas were dissected, prepared as wholemounts and immune‐labelled for Brn3a to identify surviving Brn3a+RGCs. Total numbers of surviving Brn3a+RGCs were quantified automatically and their topographical distribution was examined with the construction of isodensity maps.

Results

Seven days after IONT, treatment with saline alone or with low doses of DHF (1mg/kg, 2mg/kg) results in the loss of approximately 40% of the RGC population, whereas treatment with medium doses of DHF (4 or 5mg/kg) resulted in significant neuroprotection with loss of only 15% or 7% of the RGC population, and treatment with high doses of DHF (10 or 25mg/kg) caused loss of 26 or 29% of the RGC population.

Conclusion

Our data show that DHF has significant RGC neuroprotective effects, and that the most effective doses are 4‐5mg/kg.
A model of focal Light Emitting Diode‐Induced photoreceptor degeneration in pigmented mice
Authors: de Imperial‐Ollero Juan Antonio Miralles , Di Pierdomenico Johnny , Bernal‐Garro Jose , Villegas‐Pérez María Paz , Valiente‐Soriano Francisco Javier , Vidal‐Sanz Manuel
Published: December 2019

Purpose

To develop a new model of focal Light Emitting Diode‐Induced photoreceptor degeneration in adult pigmented mice.

Methods

In adult female C57 mice (20 g) dark adapted, the left eye was dilated with clycopentolate. Mice were anesthetized and exposed during 45 seconds to a blue (400 nm) light emitting diode (LED) (500 lux) placed 2 mm in front of the corneal apex. Animals were sacrificed 1, 3, 5 or 7 days (n = 6 each) after LED exposure, their retinas were dissected, prepared as whole‐mounts, doubly immunolabeled with antibodies against arrestin and Iba‐1 to identify cones and microglial cells and examined under fluorescence and confocal microscopy. Spectral Domain Optical Coherence Tomography (SD‐OCT, Spectralis, Heidelberg) was used to examine longitudinally in vivo the retinal thickness in both eyes at the different intervals after LED exposure.

Results

SD‐OCT eye fundus imaging with infrared reflectance allowed to document in vivo in the supero‐temporal quadrant of the LED exposed retina a rounded less reflective area that showed progressive thinning of the outer retina (approximately 75%) from 1–7 days after LED exposure. This light‐sensitive area showed by 1 day shortened cone outer segments, by 3 days a clear diminution of cone density, and by 7 days additional cone loss. The outer layers of the retina in the light‐sensitive area showed 1 day after LED exposure Iba1+ cells in the center that remained in the same location for 5–7 days. The morphology of these Iba1+ cells was dendritic at 1 day, became ameboid at 3 days and dendritic again at 5–7 days.

Conclusions

LED can be used to produce a focal phototoxic lesion in the retina. The focal lesion shows decreased retinal thickness, cone densities and an activation of microglial cells in the outer retinal layers.
The impact of oral escitalopram treatment on the function of retinal interneurons in the rat model of retinal ischemia – a pilot study
Authors: Machowicz Joanna , Wojtyniak Alicja , Pacwa Anna , Wawrzonkowski Patryk , Witek Przemyslaw , Kocot Emilia , Maciurzynski Jakub , Lewin‐Kowalik Joanna , Smedowski Adrian , Pietrucha‐Dutczak Marita
Published: December 2019

Purpose

To evaluate the impact of oral treatment with SSRI – escitalopram (EC) on the function of interneurons (IN) assessed in electroretinography.

Methods

Six Long Evans rats were treated orally with SSRI‐escitalopram (n=3) or phosphate buffered saline‐PBS (n=3) for 6 weeks daily. After 4 weeks transient elevation of intraocular pressure (IOP) was inducted in the right eye of every rat in order to induce retinal ischemia (IC). Electroretinography (ERG) was performed using Celeris device and oscillatory potentials were analysed (OPs) in 4 time points ‐ before drug administration, before IC induction and 7 & 14 days after it. After 6 weeks rats were sacrificed, retinas were isolated in order to conduct the histological assessment and cell counts. Western Blot analysis was performed in order to assess BDNF and connexin 36 content in retinas and brains.

Results

The mean peak IOP was 24 mmHg in the right eye and 12 mmHg in the left eye and was similar in treated and control groups. In both groups no loss of RGC density was noted between the eye with induced IC and the healthy one (80 ± 31 vs 76 ± 20 cells/visual field for EC and 55 ± 10 vs 55 ± 11 for PBS; p > 0.05). In the functional measurements in the EC group amplitudes of all scotopic OPs (OP1‐5) were significantly higher 14 days after IC induction when compared to control group (p < 0.05), where deep disturbance of IN function was observed, specifically for OP2‐4, expressed in significant reduction of OP amplitudes (p < 0.05). Similar changes were not observed in photopic conditions.

Conclusions

Oral treatment with EC prevents desynchronization of retinal IN function during ischemic conditions in a rat. Observations presented above may become crucial for new therapeutic methods for vascular pathologies of the retina.
Eyelid Disorders Highly Prevalent in Ophthalmology Practice; Results From a Large International Epidemiological Study in Eleven Countries
Authors: Doan Serge , Zagorski Zbigniew , Palmares Jorge , Yagmur Meltem , Kaercher Thomas , Benitez Del Castillo José Manuel , Van Dooren Bart , Jonckheere Paul , Jensen Pk , Maychuk Dmitry Yurevich , Bezditko Pavel Andreevich
Published: December 2019

Purpose

Anecdotal evidence suggests that eyelid disorders are common, although estimates of its prevalence vary. A cross‐sectional epidemiological survey was conducted among patients attending routine ophthalmological consultations to determine the prevalence of eyelid disorders, Meibomian Gland Dysfunction (MGD) and related pathologies (in particular ocular surface disease).

Method

During the consultation a quality of life questionnaire and a clinical examination were completed by the ophthalmologist. In eleven countries, 349 investigator ophthalmologists were recruited who provided data from 6525 patients.

Results

Patients were predominantly female (61.6%), mean age 57.0 ± 17.6 y. Eyelid disorders were diagnosed in 78.3% of patients and were statistically associated with atopic dermatitis, seborrheic dermatitis, dry eye, age‐related macular degeneration, diabetes, cataract, allergy and MGD. Eyelid abnormalities were identified in 38.5% of patients; abnormalities of the eyelid margin in 59.8%, and abnormal meibomian gland secretion in 34.5%. Conjunctival or corneal abnormalities were observed in 64.9% and 27.9% of patients respectively. MGD was diagnosed in 54.0% of patients and was statistically significantly associated with the presence of eyelid disorders and eyelid margin abnormality. Dry eye was diagnosed in 61.2% of patients and was concomitant with MGD in most cases. Most patients reported some degree of impairment of vision and daily/work activities. These effects on daily life were associated with the presence of MGD. Impact on contact lens usage and on emotions and quality of sleep were also reported.

Conclusion

In conclusion, eyelid disorders were highly prevalent in this clinic population. Routine ophthalmological consultations may provide a useful opportunity to improve patients’ quality of life and to modify topical therapy where this is an aetiological factor in eyelid disorders.
Recurrent pyogenic granuloma (Lobular Capillary Haemangioma) of the eyelid in a breast‐feeding patient
Authors: Mansoor Nyaish
Published: December 2019

Pyogenic granuloma, also known as lobular capillary haemangioma, is a benign vascular tumour which is commonly found in children, young adults and pregnant women. In pregnant women they are usually found on mucosal surfaces such as the gums and are thought to be related to the hormonal changes associated with gestation. Here we describe a case of a three‐times recurrent pyogenic granuloma in the unusual location of the eyelid in a 34‐year‐old breast‐feeding patient. The patient required three excisional procedures. It was felt that the likely cause of the growth was due to hormonal changes related to the prolonged period of lactation. To date only three other cases have been reported of pyogenic granuloma in the gestational or post‐partum period in the eyelid with this being the first case in a breast‐feeding patient to the best of our knowledge. This case highlights the difficulty in managing these lesions and contributes further evidence towards the hypothesised relationship between the hormonal changes associated with pregnancy, breast‐feeding and this lesion.
Effectiveness of selective laser trabeculoplasty in glaucoma patients: a 6 years follow up study
Authors: Aristeguieta Indira , Ayala Eleonora , Gonzales‐Farro Karla , Anton Alfonso , Beltran‐Agullo Laura , Morilla Antonio
Published: December 2019

The use of laser trabeculoplasty (SLT) to lower intraocular pressure (IOP) has provided an alternative strategy to treat open angle glaucoma (OAG) or ocular hypertension (OHT). SLT lowers IOP by enhancing aqueous humor outflow through the trabecular meshwork. It induces less coagulative damage than argon laser trabeculoplasty. The effect of SLT diminishes over time and some patients may need more treatment or surgery.

Purpose

To evaluate long‐term effectiveness of SLT in OAG/OHT.

Methods

Retrospective cohort study. All patients with OAG/OHT treated in 2012 with 180º SLT were included. Patients with <1 year of follow up were excluded. Following SLT, patients were examined at 6, 12, 24, 36, 48, 60 and 72 months. In each visit IOP was measured, and fundus and anterior segment were examined. Structural images and visual fields were performed to asses glaucoma progression.

Results

Seventy‐eight eyes of 49 patients were included. Mean age was 65.2 ± 12.2 years old. Forty two eyes had OAG, 6 pseudo‐exfoliation glaucoma, two pigmentary glaucoma, two aphakic glaucoma and 26 had OHT. The mean follow‐up was 5.2 ± 1.4 years. Mean previous IOP was 21.2 ± 3.7 mmHg. After treatment, and excluding patients who required surgery, IOP had significantly decreased to 17.1 ± 3.2 mmHg at one year (n = 73; p < 0.001) and to 17.4 ± 3.5 mmHg (p < 0.001) at 6 years of follow‐up (n = 41). The number of drugs used was 2 ± 1.1 before treatment and 1.9 ± 1.2 (n = 41; p = 0.55) after 6 years. A total of 35 eyes (27.3%) needed more than one SLT session to achieve the desired IOP and 18 eyes (23.1%) needed glaucoma surgery in a mean time of 2 years after the first SLT. None of the patients had major complications related to SLT treatment.

Conclusion

Although the effect of SLT decreases with time, our study shows that it can be an effective technique to significantly lower IOP after 6 years of follow up.
The grading of risk factors for diabetes based on early loss of colour and flicker sensitivity
Authors: Bastaki Qais , Rodriguez‐Carmona Marisa , Barbur John L
Published: December 2019

Purpose

The purpose of this study was to identify and grade risk factors (in clinically normal subjects) that can lead to diabetes based on early changes in chromatic sensitivity and rod‐ and cone‐mediated vision.

Methods

A group of ‘high‐risk’ subjects (n = 82) were recruited for this study. All attended a healthcare centre for detailed vision assessment, in addition to other diagnostic and screening tests. The inclusion criteria required subjects to have at least three or more recognised risk factors for diabetes. The factors examined included HbA1C (>5.7), high blood pressure, smoking history, high BMI, family history of diabetes, FPG levels (>100 mg/dl), age (>45 years), unhealthy diet and lack of exercise. In addition, Visual Acuity, Functional Contrast Sensitivity, rod and cone sensitivities and red‐green (RG) and yellow‐blue (YB) colour thresholds were measured in each subject using the Advanced Vision and Optometric Tests (www.avot/city.ac.uk).

Results

Each of the risk factors for diabetes listed above was examined to establish its effects on RG and YB colour thresholds and the loss of rod and cone sensitivity. Subjects with hypertension had higher RG (p = 0.009) and YB (p = 0.003) colour thresholds and increased contrast thresholds for rod‐ (p = 0.04) and cone‐mediated (p = 0.006) vision. In addition, age (>45) (p = 0.02) and the lack of exercise (p = 0.04) caused worsening of YB colour vision. Lack of exercise is also linked to a statistically significant difference (p = 0.02) in cone mediated vision. Neither family history, nor BMI or unhealthy diet had significant effects on colour or rod‐ and cone‐mediated flicker sensitivity.

Conclusions

Subjects at risk of developing diabetes can have significant loss of RG and/or YB colour vision and rod and cone‐mediated flicker sensitivity. The most significant risk factors according to this study are high blood pressure, lack of exercise and age. Although these findings are of immediate clinical interest, it remains to be established how these factors are correlated and the neural changes that can be linked directly to the worsening of colour vision and rod and cone‐mediated flicker sensitivity.
Candidate gene analysis of germline variants in Finnish patients with juvenile open‐angle glaucoma
Authors: Järvinen Reetta‐Stiina , Tadji Abdessallam , Repo Pauliina , Liuska Perttu , Harju Mika , Kivelä Tero , Turunen Joni
Published: December 2019

Purpose

Juvenile open‐angle glaucoma (JOAG) is a rare type of glaucoma diagnosed in children older than 3 years and adults less than 40 years of age. Predisposition to JOAG is generally inherited in an autosomal dominant pattern. Pathogenic MYOC germline variants are reported in 8‐36% of patients. Rarer pathogenic variants in other genes could also predispose to JOAG. Our aim was to detect disease‐associated germline variants in glaucoma candidate genes in Finnish patients with JOAG.

Methods

We studied 46 unrelated patients with JOAG treated between 2010 and 2018 at the Department of Ophthalmology, Helsinki University Hospital, Finland. We first sequenced all exonic regions and flanking splice sites of MYOC using Sanger sequencing. In 42 patients without a pathogenic MYOC germline variant, we then performed whole exome sequencing (WES) to investigate variants in 17 glaucoma‐related genes.

Results

Four probands had a likely pathogenic variant in MYOC: c.1109C>T, p.(Pro370Leu), 1130C>T p.(Thr377Met), 1132G>A p.(Asp378Asn), and c.1204G>A, p.(Val402Ile). Three of these patients had a family history of dominantly inherited JOAG. One patient and his mother with JOAG had a loss‐of‐function variant in the FOXC1 gene, c.G366A, p.(Trp122Ter). One patient with sporadic glaucoma had a homozygous likely pathogenic variant in the LTBP2 gene, c.G3938A, p.(Cys1313Tyr). The frequency of the variant carriers in Finns is 0.03% (the gnomAD database). The frequency of MYOC variants was 9% (4/46; 95% CI, 2‐21). The detected genetic variants explained 13% (6/46; 95% CI 5‐26%) of JOAG in our patient series.

Conclusions

Genetic variants in known JOAG‐associated genes seem to be less frequent in Finnish patients, compared to other reported populations. Because of the specific population history of Finland, the genetic background of Finns differs from other European populations. Therefore, it might be possible to identify novel glaucoma genes through our JOAG series in the future.
Germline variants in the MBD4 gene are rare in patients with uveal melanoma
Authors: Repo Pauliina , Jäntti Johannes , Järvinen Reetta‐Stiina , Täll Martin , Raivio Virpi , Kivelä Tero , Turunen Joni
Published: December 2019

Purpose

The mutation profile of uveal melanoma (UM) is unusual as these tumors generally have very few somatic events. Eight genes are recognized as drivers of UM tumorigenesis, typically consisting of one mutually exclusive mutation in GNAQ, GNA11, PLCB4 or CYSLTR2 combined with one mutually exclusive mutation in EIF1AX, SF3B1, SRSF2 or BAP1. Germline variants predisposing to UM have so far been described only in BAP1. Recently, four patients with UM were found with germline loss of function (LOF) variants in the methyl‐CpG binding domain 4 (MBD4) gene that was suggested to be a UM predisposition gene. Loss of functional MBD4 induces a hypermutated profile, making the tumor more susceptible to immune checkpoint inhibitors. We investigated MBD4 variants in patients with UM to identify pathogenic variants and to estimate their clinical relevance.

Methods

Sanger sequencing of MBD4 in 440 Finnish patients with uveal melanoma diagnosed from 2010 to 2017.

Results

Eight rare (minor allele frequency in gnomAD Fin <0.5%) MBD4 missense variants were identified in 16 patients. One of them was likely pathogenic. The UM has not metastasized. The frequency of likely pathogenic MBD4 variants in Finnish patients with UM was 0.2% (95% CI, 0.01–1.3). No LOF variants were found. The frequency of LOF variants in the general population in Finland is 0.05%, according to the gnomAD database, suggesting one should occur by chance in every 2000 patients with UM.

Conclusions

MBD4 variants do not seem to predispose to UM in Finland. Somatic loss of MBD4 function might still modify the tumor phenotype through accumulating mutations and changing the response of the tumor to immune checkpoint inhibitors. However, the utility of germline MBD4 sequencing is low.
Improvement and validation of high precision ocular oximetry using a convolutional neural network algorithm and a phantom eye
Authors: Desroches Joannie , DePaoli Damon , Lapointe Nicolas , Paulin Catherine , Tossou Prudencio , Sauvageau Patrick , Sauvageau Dominic , Côté Daniel
Published: December 2019

Retinal oximetry is a non‐invasive imaging technology that enables the measurement of oxygen saturation (StO2) in the eye fundus. The goal of this research was to validate a convolutional neural network (CNN) algorithm designed to calculate and improve the precision of StO2 measurements from diffuse reflectance spectra (DRS) taken on the optic nerve head (ONH). Zilia’s multi‐wavelength retinal oximetry device was used to acquire experimental spectra from the ONH which allowed us to simulate reasonable digital spectra replicates with known absorber concentrations. These spectra were used to train a novel machine learning algorithm based on CNN. The device was then used to acquire diffuse reflectance spectra on several ONH‐mimicking liquid optical phantoms (phantom eye) with dynamic oxygenation cycles between 0% ‐ 100% in order to validate the improvements of this CNN on experimental data. Measurements were made simultaneously with gold standard devices for comparison. The procedure was then repeated with several cataract‐simulating contact lenses integrated in the optical path to show the robustness of oximetry measurements. We found good agreement in StO2 measurements between the results obtained with the Zilia device using the CNN algorithm and the gold standard references in all phantom cases. Applying the various algorithms to data acquired on the validation phantom show the marked improvements in using the CNN on experimental data, validating its high potential for clinical use. We specifically show strong robustness in precision, even when cataract‐simulating lenses were used. We present further validation that the oximetry device and CNN algorithm produces reliable, precise measurements even under conditions where blood volume fractions vary, optical scattering changes, and cataract‐simulating contact lenses are included.
Retinal thickness of the triple‐transgenic mice model of Alzheimer\’s disease at the age of one month
Authors: Bernardes Rui , Ferreira Hugo , Martins João , Moreira Paula I. , Castelo‐Branco Miguel , Ambrósio António F. , Serranho Pedro
Published: December 2019

Purpose

In this work, we aimed to assess the difference in thickness of the retina of the triple‐transgenic mice model of Alzheimer’s disease (3xTg‐AD), compared to controls (wild‐type ‐ WT), at the age of one month.

Methods

Mice’s retinas were imaged by optical coherence tomography (OCT) using the Phoenix Micron IV OCT (Phoenix Research Labs, USA) to produce 512 B‐scans of 512 A‐scans each. All right eyes of 45 3xTg‐AD and 46 WT mice were imaged in vivo, and all scans were performed horizontally centred in the optic disc and vertically above it. All mice were weighted at the scan time. A software was developed to determine the inner limiting membrane and the photoreceptor‐retinal pigment epithelium interface, automatically, to produce a detailed thickness map of 512 × 512 values, later split into 3x3 regions. The average thickness of each region and the average of the entire imaged area were computed. All processing, software development and statistical analyses were performed using Matlab R2019a (The Mathworks Inc, USA).

Results

The Kolmogorov‐Smirnov normality test was applied to all measures. Since the majority failed the normality assumption, the Mann‐Whitney test was used to determine differences between groups. No statistically significant differences were found between groups for the weight (p‐value=0.9536; m(sd): 14.84(2.71) grams for 3xTg‐AD and 14.88(2.58) grams for WT). A strong statistically significant difference (p‐value < 0.001) was found between the thickness of the retina of the two groups for all nine regions and the average retinal thickness, with the 3xTg‐AD mice presenting a thinner retina ‐ average values for the entire imaged area of 290.26(7.15) (m(sd)) microns compared to the WT (302.20(4.08)).

Conclusions

The 3xTg‐AD mice present a statistically thinner retina regarding the control group, at the age of one month, even though no statistically significant differences were found between groups for the weight.
Solo surgeon strabismus surgery technique
Authors: Feng Lo Phey , Lockwood Alastair , Evans Anthony , Thornton Richard , Townsend Dominic
Published: December 2019

Background

Strabismus surgery is frequently undertaken solo without surgical assistants, requiring alternative methods for accurate muscle isolation and placement. We aim to describe a novel single surgeon technique during recti muscle surgery in the management of horizontal strabismus.

Methods

After isolating the recti muscle on a hook, the muscle is secured with a double armed 6‐0 Vicryl (Ethicon) on a spatulated needle at the point of insertion. A partial thickness bite is taken at the muscle belly followed by two full thickness locking bites at the superior and inferior poles of the muscle. For recessions, the 6‐0 suture is placed behind the blades of the Cook speculum which acts to keep sutures away from the area and provides some traction opposite to that from the Moody forceps. This allows good visualisation and allows the surgeon to mark the suture placement site. Tucking the suture behind the Cook speculum also helps with resection but there is less of a traction element required here.

Results

This technique has been proven to be effective in allowing the surgeon to operate without an assistant. There have been fewer lists cancellations due to absences and lack of an assistant. Furthermore postoperative results have been comparable to those operated with an assistant.

Conclusion

The advantages of this technique are its ease of execution without having to rely on extra instrumentation. It allows the solo surgeon to operate without having to depend on an assistant thereby increasing efficiency and reducing waiting list times. It is also a very handy tip and easily taught to trainees.

Reference

Winter TW, Olson RJ et al. Resident and Fellow Participation in Strabismus Surgery: Effect of level of training and number of assistants on operative time and cost. (2014) Ophthalmology, 121(3), 797‐801.
Refractory atypical corneal lesions with or without extension onto the conjunctiva responding to Acanthamoeba treatment
Authors: Dubois Pauline , Weiss Azzam , Valyi Zsuzsanna , Le Aurelie , Bradly Kenza , Willermain François , Caspers Laure
Published: December 2019

Purpose

Acanthamoeba keratitis (AK) is a sight‐threatening infection classically linked to contact lens wear. Starting as a non‐specific unilateral epithelial irregularity like punctate or pseudo‐dendritic lesions, AK can evolve to a ring‐shaped stromal infiltrate with risk of corneal melting. Radial keratoneuritis may appear. Diagnosis relies on protozoan identification by culture with direct exam and PCR analysis. Acanthamoeba can also be demonstrated by in vivo confocal microscopy (IVCM). Early phase AK is treated with a combination of topical amoebicides. We report three atypical cases of suspected AK.

Methods

Retrospective report of three women with unilateral atypical corneal lesions, two of them extending to the conjunctiva. Slit lamp photographs, corneal oct and confocal microscopy will be presented.

Results

Three patients, two women in their thirties and one in her sixties, consulted for chronic ocular discomfort unsuccessfully treated by topical antibiotics and corticosteroids for months to years. No history of contact lens wear or water exposure was reported. Two had visual acuity (VA) at 20/20 and one a variable VA for 4 years. Slit lamp examination showed an atypical superficial well delimitated linear lesion across cornea and conjunctiva. In all patients, successive examinations had revealed a moving and migrating character of the refractory lesions to topical antibiotics and corticosteroids. All had a rapid response to Polyhexamethylenebiguanide (PHMB) and propamidine (Brolene) and healed without stromal opacification in a few weeks. Although corneal scrapping cultures remained negative, two of them realized an IVCM with signs of AK and all responded rapidly and completely to amoebicide drops supporting the diagnosis of AK.

Conclusions

These cases show a particularly atypical involvement of corneal and conjunctival refractory lesions responding very well to PHMB and Brolene suggesting an AK origin.
Pupil irregularity after ultrasound ciliary plasty in glaucoma treatment
Authors: Bolek Bartlomiej , Wylegala Adam , Mazur Robert , Wylegala Edward
Published: December 2019

Purpose

The aim of a study is to evaluate pupil irregularity eyes after transscleral Ultrasound Ciliary Plasty. How dimensions of the pupil are changing after UCP procedure.

Setting/Venue

Clinical Department of Ophthalmology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland.

Methods

Twenty two patients with primary and secondary refractory glaucoma were enrolled to ultrasound ciliary plasty procedure. The pupil size was measured at the widest dimension in which irregularity was observed. Measurements were performed before the procedure, 6 and 12 months after. Analyzed pupil parameter was obtained with SS OCT CASIA 2.

Results

Preliminary results reveal that there is no significant difference in pupil widest dimension after UCP procedure comparing size before (4.03 ± 0.56 mm), 6 months (4.15 ± 0.61 mm; p = 0.432) and 12 (4.02 ± 0.56 mm; p = 0.647 ) months after.

Conclusion

UCP seems to have influence on pupil size. However we are observing pupil irregularity few months after procedure, the results are not significant.
Histology of myopic posterior scleral staphylomas
Authors: Jonas Jost , Ohno‐Matsui Kyoko , Holbach Leonard , Panda‐Jonas Songhomitra
Published: December 2019

Purpose

Since histomorphometric descriptions of posterior scleral staphylomas, although forming a major part of myopic maculopathy, have been scarce so far, we histomorphometrically examined scleral staphylomas in enucleated human eyes.

Design

Histomorphometric study.

Methods

Using light microscopy, we examined sagittal histological sections of human globes enucleated due to malignant choroidal melanomas or secondary angle‐closure glaucoma.

Results

Out of 246 globes included into the study, posterior scleral staphylomas were detected in 10 eyes (mean length: 31.4 ± 3.0 mm; range: 28.0–37.0 mm). In the staphylomatous region in the study group as compared with the corresponding region of a control group adjusted for age and axial length, scleral thickness was significantly lower (109 ± 25 µm versus 319 ± 161 µm; p = 0.001). The study group in the staphylomatous region as compared to the highly myopic control group in the corresponding region did not differ significantly in retinal pigment epithelium (RPE) cell density (19.6 ± 4.9 cells/300 µm versus 21.1 ± 5.7 cells/300 µm; p = 0.84) and RPE height (8.2 ± 3.0 µm versus 6.0 ± 2.5 µm; p = 0.11), Bruch´s membrane (BM) thickness (3.5 ± 1.1 µm versus 3.9 ± 2.1 µm; p = 0.63), and choriocapillaris thickness (5.0 ± 2.7 µm versus 4.1 ± 2.7 µm; p = 0.50) and density (164 ± 99 µm versus 226 ± 38 µm; p = 0.13). All staphylomatous regions showed a localized BM defect.

Conclusions

Marked scleral thinning and spatially correlated BM defects histologically characterized myopic scleral staphylomas, while thickness and density of the choriocapillaris, RPE and BM did not differ significantly between staphylomatous versus non‐staphylomatous eyes in the respective regions. These findings support the notion that a locally reduced scleral resistance against a backward pushing BM led to a local scleral outpouching. The outpouching‐associated increase in curvature length may stretch BM with the sequel of a localized BM rupture
Choriocapillaris thickness and density in high myopia
Authors: Holbach Leonard , Jonas Jost , Panda‐Jonas Songhomitra
Published: December 2019

Purpose

Myopic axial elongation is associated with choroidal thinning in general. We examined whether the thickness of the choriocapillaris decreases in relationship to axial length.

Methods

Using light microscopy, we measured thickness and density of the choriocapillaris in various ocular regions on sagittal histological sections of human globes enucleated due to malignant choroidal melanomas or secondary angle‐closure glaucoma.

Results

The study included 75 globes with a mean age of 62.6 ± 17.0 years (range: 24–88 years) and a mean axial length of 27.8 ± 3.8 mm (range: 22.0–37.0 mm). The choriocapillaris was significantly (p = 0.008) thicker at the posterior pole (6.8 ± 6.0 µm) than at the posterior pole‐equator midpoint (5.0 ± 3.8 µm), where it was thicker (p = 0.03) than at the equator (4.0 ± 3.4 µm), with no significant (p = 0.16) difference from there to the ora serrata (4.6 ± 3.8 µm). Choriocapillaris thickness was not significantly associated with axial length, neither at the posterior pole (p = 0.83), posterior pole‐equator midpoint (p = 0.79), equator (p = 0.99) or ora serrata (p = 0.18). Mean choriocapillaris density was 216 ± 56 µm/300 µm at the posterior pole, 193 ± 64 µm/300 µm at the posterior pole‐equator midpoint, 174 ± 73 µm/300 µm at the equator, and 196 ± 66 µm/300 µm close to the ora serrata. The difference in choriocapillaris density between the posterior pole and the equator was significant (p = 0.02). Choriocapillaris density was not significantly associated with axial length (posterior pole: p = 0.29; posterior pole‐equator midpoint: p = 0.68; equator: p = 0.76; ora serrata: p = 0.61). At the posterior pole, choriocapillaris density was associated with a higher RPE cell height (p = 0.02) and higher RPE cell density (p = 0.02).

Conclusions

Choriocapillaris thickness and density, decreasing from the posterior pole to the fundus periphery, were not significantly associated with axial length. Higher choriocapillaris density was associated with higher RPE cell height and density. These findings may be of interest for the understanding of pathologic myopia.
Refraction in eyes filled with silicone oil
Authors: Kanclerz Piotr , Grzybowski Andrzej , Leisser Christoph , Lipowski Pawel
Published: December 2019

Purpose

Cataract development is common in phakic eyes filled with silicone oil (SO), necessitating subsequent cataract removal. This study evaluated the refractive outcome in eyes filled with SO undergoing phacoemulsification cataract surgery (PCS).

Methodology

This retrospective study evaluated patients with SO tamponade who were scheduled for PCS.

Results

Subjects (n = 26) were followed‐up for 29.5 ± 13.9 months after cataract surgery. The median spherical equivalent refraction (SER) was +5.3 D (interquartile range [IQR] +2.9 to +6.7) before PCS, and +3.4 D (IQR +2.0 to +4.4) after PCS. Within the follow‐up period retinal reattachment after SO removal was achieved in 15 out of 26 eyes (57.7%). In 13 eyes assessment of refraction after SO‐removal was possible, and showed a myopic shift of −4.6 D (IQR −2.9 to −7.3) in the SER. After SO removal, five of 13 eyes (38.5%) were within ±1.0 D of the target refraction, while nine out of 13 eyes (69.2%) were within ±2.0 D.

Conclusion

The refractive outcome after PCS for eyes filled with SO is less predictable than that for normal eyes. Optical biometry should be performed before vitrectomy with SO administration when possible. Some of the eyes undergoing silicone oil injection may require long‐term tamponade.
Transduction pattern of adeno‐associated viruses in the trabecular meshwork and anterior‐segment structures in a rat model of ocular hypertension
Authors: Lee Si Hyung , Woo Sang Earn , Park Tae Kwann
Published: December 2019

Purpose

To investigate transduction patterns of self‐complimentary adeno‐associated virus (scAAV) serotype 2, 5, and 8 in trabecular meshwork (TM) and anterior segment structures of ocular hypertensive (OHT) rat models.

Methods

We assessed transduction efficiencies of scAAV 2, 5, and 8 in the anterior‐segment structures of the eyes of SD rats with OHT by circumlimbal suturing, followed by intracameral injection of scAAV2, 5, or 8 packaged with EGFP, and compared with the control. Expression level of receptors for scAAV2 (perlecan and syndecan), scAAV5 (2, 3‐linked sialic acid), and scAAV8 (67kDa laminin receptor) was analyzed by using immunohistochemistry and quantitative PCR.

Results

The transduction of scAAV2 and 5 in the TM of OHT rats was markedly enhanced after 1 month, and transduction of scAAV5 was more efficient than that of scAAV2; transduction of scAAV8 into the TM did not occur. The transduction of scAAV2, 5, and 8 was enhanced in the ciliary body, iris, and corneal endothelium of the OHT eyes for 3 months. The expression levels of receptors for scAAV2 and scAAV5 were significantly increased in the OHT compared with control eyes.

Conclusions

The results showed that scAAV 2 and 5 effectively target the ciliary body and TM in OHT eyes, and OHT related changes in anterior segment structures enhance scAAV transduction.
The tear film cytokine profile is altered in congenital Aniridia
Authors: Sommer Landsend Erlend
Published: December 2019

Increased levels of inflammatory cytokines in the tear fluid have been found in patients with dry eye disease (DED). Dry eye disease is highly prevalent in congenital aniridia and correlates with severity of aniridia associated keratopathy (AAK). As inflammation can damage the corneal epithelium, DED may initiate and worsen AAK. Additionally, inflammation also characterizes AAK and might exacerbate DED, creating a vicious circle. We carried out an extensive analysis of inflammatory cytokines in the tear fluid of aniridia patients and control subjects. The results were correlated with several clinical parameters, including tests for DED and meibomian gland dysfunction (MGD). The concentration of a number of pro‐inflammatory cytokines was significantly elevated in tear fluid from aniridia patients. Increasing level of these cytokines was related to parameters for MGD, including atrophy of meibomian glands, and shorter break‐up time of the tear film. Increased inflammation of the ocular surface may be a factor in the development of MGD in aniridia patients and explain the high prevalence of MGD and DED in these patients.
New insights in the genetic and pathophysiology of dominant optic atrophy
Authors: Lenaers Guy
Published: December 2019

Inherited Optic Neuropathies are blinding diseases related to mitochondrial dysfunctions in retinal ganglion cell (RGC). There are two main forms: the Leber Hereditary Optic Neuropathy (LHON) related to mutations in the mitochondrial genome, and the Kjer dominant optic atrophy (DOA) related to mutations in nuclear genes. Since the initial discovery of the OPA1 gene as the major gene causing DOA, the use of NGS disclosed many novel genes responsible for DOA. Beyond the genes recently identified involved in mitochondrial dynamics, we identified novel genes involved in other mitochondrial functions that are crucial for RGC physiology. We report here the pathophysiological analyses of their involvement in mitochondrial physiology and metabolism. These data are shedding novel lights on DOA pathophysiology, beyond mitochondrial dynamics, as novel culprit mechanisms responsible for RGC degeneration, which will condition the design of future therapeutic approaches.
Chromatin dynamics, DNA‐binding transcription factors and lens differentiation
Authors: Cvekl Ales
Published: December 2019

Purpose

Lens differentiation is an advantageous model to study how chromatin structure and dynamics (“open” and “closed” chromatin) regulates gene expression of both regulatory factors and proteins needed for intricate lens fiber cell structure and function. Our purpose was to map and explain dynamic changes in local chromatin structure of genes during lens differentiation at genome‐wide level.

Methods

ATAC‐seq experiments were conducted using epithelia and fibers from E14.5 and newborn (P0.5) mouse lenses. RNA‐seq data from similar samples were included in the analysis.

Results

Open chromatin changes were defined through identification of differentially accessible regions coupled with differential gene expression during lens differentiation. Lens‐specific regulatory regions are shown using ES cells, forebrain, and liver. Two pathways were identified: epiE14.5 → fibE14.5 → fibP0.5 (path1) and epiE14.5 → epiP0.5 (path2). Unbiased cis‐motif analysis of “open” regions corresponding to promoters and enhancers revealed the cis‐regulatory principles of lens differentiation via known (e.g. AP‐1, Ets, Hsf4, Maf, and Pax6) and novel (e.g. CTCF, Tead, and NF1) motifs.

Conclusions

The current data support a general model of dynamic changes in open chromatin associated with transcriptional activities of functionally related genes that required for lens fiber cell differentiation and epithelial maturation. Together, the data pave the road for detailed studies of lens‐specific enhancers, identification of gene regulatory networks underlying lens morphogenesis, and identification of cataract‐causing mutation in non‐coding regulatory sequences.
Improving corneal nerve regeneration: initial results of a novel regenerative agent
Authors: Gallar Juana
Published: December 2019

It is well stablished that nerve deficit in the cornea leads to an imbalance in trophic factors required to maintain a healthy corneal tissue. This deficit is clinically manifested as impaired epithelial repair and wound healing, and eventually stromal scarring and ulceration, leading to a greater risk of transplant failure. Thus, corneal trophic environment must be restored by first promoting an adequate corneal nerve regeneration after transplant, although nowadays there is no approved neuro‐regenerative therapy for the cornea.

A plethora of cytokines, chemokines and growth factors influence neuron survival and axon regeneration after lesion, most of them produced locally by Schwann cells at the distal nerve stump after nerve axotomy. In ARREST BLINDNESS work package 7, the efficacy of topical treatment with several cytokines, chemokines and trophic factors to promote corneal axon regeneration and the restoration of corneal sensory and trophic functions has been tested in an experimental model of surgically‐induced neurotrophic deficit, induced by performing a corneal stromal flap in the guinea‐pig. Using NGF as a positive control, protein neublastin, a member of the glial cell line derived neurotrophic factor family has been identified as the most effective factor to increase nerve regeneration after corneal lesion.

(Supported by ARREST BLINDNESS, a project funded by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No 667400)
Targeting ion channels to treat corneal neuropathic pain and dry eye
Authors: Gallar Juana
Published: December 2019

Ocular sensations and pain results from the activation of peripheral nerve endings of trigeminal ganglion neurons whose sensitivity to different types of stimulus depends on the expression in their membrane of specific ion channels involved in sensory transduction. TRPM8 channel provides sensitivity to temperature changes and osmolarity; TRPV1, TRPA1 and ASIC channels, to chemical and heat stimuli, and Piezo2 channels, to mechanical forces. Other ion channels present in nerve endings as Cav, Nav, Kv, HCN and (2PD)K+ modulate their excitability and contribute to encode the stimulus. After nerve injury, sensory nerves firing is altered due to changes in the expression/activity of both transducing and excitability‐modulating ion channels, being this altered activity the basis of neuropathic pain. Then, transducing and encoding ion channels are potential molecular targets to modulate neuropathic nerve activity. Besides the classical use of drugs modulating the activity of TRPM8, TRPV1, Ca2+, Na+ or Kv channels, new approaches like the use of small molecule photoswitches (optopharmacology) are promising tools to alternatively block and unblock those ion channels involved in corneal neuropathic pain and dry eye.

(Supported by grants SAF‐2017‐83674‐C2‐2‐R and 1‐R from Agencia Estatal de Investigación, Spain, and ERDF, EU, and PROMETEO/2018/114 from Generalitat Valenciana, Spain).
Genomics and molecular mechanisms in glaucoma and anterior segment abnormalities
Authors: Jamieson Robyn
Published: December 2019

Ocular anterior segment disorders have a significant impact on vision and may lead to glaucoma in over 50% of cases. They occur due to a complex interplay of developmental and genetic factors, and there are often marked phenotypic overlaps and genetic heterogeneity. Disorders of the anterior segment of the eye encompass a variety of clinical presentations including aniridia, Axenfeld and Rieger anomalies, primary congenital glaucoma, Peters anomaly, and there are a number of syndromal associations. Several genotype‐phenotype correlations are present, and genomic approaches have facilitated broadening of known phenotypes and led to identification of new anterior segment disease genes and pathways. Key disease genes include FOXC1, PITX2, CYP1B1, FOXE3, and PAX6, and there are a number of newly identified and less frequently reported disease genes including GJA8, CPAMD8, PXDN and COL4A1. Whole exome and whole genome sequencing approaches facilitate genetic diagnosis in these genetically heterogeneous disorders. These approaches, in combination with cellular and animal model studies, assist in elucidation of novel disease genes and molecular mechanisms contributing to glaucoma and anterior segment abnormalities.