bluuebunny/crossref_metadata_2025 huggingface dataset:
Muller glia as endogenous neuroprotectors of the retina
Authors: Vecino Elena
Published: December 2019

Endogenous cellular protective mechanisms may help in the development of therapies in order to achieve progress in the treatment of neuroprotection of the retinal cells. Exposure to high IOP induces changes in the endogenous neurotrophins from different retinal cells. In particular we found a transient increase of BDNF synthesis by RGCs after IOP increase that could be implicated in their neuroprotective transient responses endogenously or by acting through Müller glia. A possible proposed mechanism of action on Müller glia is through inhibiting the osmotic swelling and by up regulating the glutamate/aspartate transporter (GLAST) and Glutamine Synthetase (GS) expression in Müller glia. Moreover, we have demonstrated that Müller glia protects RGCs by several secreted factors as determined by proteomic analysis from their condition media. We will present the last studies showing how Müller glia protects RGCs.
The cis‐regulatory logic of photoreceptors and bipolar cells
Authors: Corbo Joseph
Published: December 2019

Multicellular organisms evolved via repeated functional divergence and subspecialization of transcriptionally related, but distinct sister cell types. In this talk, I describe the cis‐regulatory logic of two canonical sister cell types in the retina: photoreceptors and bipolar cells. Although these cell types have highly divergent transcriptional profiles and open chromatin maps, they share remarkably similar cis‐regulatory grammars. I present evidence that the presence/absence of a single key transcription factor binding site motif played a key role in the evolutionary divergence of the bipolar transcriptome from that of photoreceptors.
Ocular thermography in normal subjects
Authors: Moussa Sarah
Published: December 2019

In healthy subjects, corneal surface temperature measured by the Ocular Surface Thermographer TG‐1000 (Tomey, Germany) does not change diurnally and is warmer nasally than centrally and temporally during the interblinking interval. This leads to the assumption that diurnal changes of corneal temperature indicate ocular surface abnormality or corneal pathology.
Investigations of Uveitis
Authors: James Teifi
Published: December 2019

Teifi James discusses an investigation strategy explaining how to investigate patients presenting with uveitis and associated clinical problems. Starting with the history and the clinical examination he gives a logical and straightforward progression of investigations which are chosen according to the clinical situation. He will explain the wisdom of first doing simple investigations like dipstick testing of urine, chest X‐ray and Full Blood Count, but explain when and why it is appropriate to conduct more elaborate tests. Think before requesting any investigation – why am I doing this test?
Pearls and pitfalls
Authors: Kivelä Tero
Published: December 2019

The speaker will highlight some pearls and pitfalls in statistics that both authors and readers benefit from knowing, based on his personal experience as a writer, reviewer and editorial board member. The items discussed, based on examples from recent literature, will include: (1) How to avoid giving a false impression of precision when reporting key results, (2) How to communicate effect size; (3) How to differentiate statistical from clinical significance, (4) How to communicate statistically non‐significant results, and (5) How to recognise multiple comparisons and adjust for them. Clear reporting of basic statistics is not difficult as long as one is aware of some basic rules. Putting them into action may improve your manuscripts and reading skills when scanning published evidence to base your practice on.
Ex vivo expansion of human labial mucosal epithelium for corneal surface reconstruction
Authors: Gerasimov Maxim , Borzenok Sergey A. , Malyugin Boris E. , Ostrovskiy Dmitriy S.
Published: December 2019

Purpose

To achieve ex vivo expansion of human labial mucosal epithelium using the explant method and simplified formulation of the culture media.

Methods

Labial mucosa was obtained from six patients during conjunctival fornix reconstruction after signing informed contest. The substantia propria was severed, and the remaining tissue was into 1 × 1 mm explants. Explants were cultured in EpiLife (0.06 mM Ca) and DMEM/F12 (1:1) (1.05 mM Ca) media supplemented with 5% fetal bovine serum, hydrocortisone 5 µg/mL, human recombinant epidermal growth factor (hrEGF) 10 ng/ml, insulin 5 µg/ml, and standard antifungal‐antibiotic. Besides routine monitoring, primary cells were double stained with anti‐p75/p63, anti‐integrin b1/vimentin, and anti‐ZO‐1/CK10 antibodies.

Results

Explant outgrowths had cobblestone epithelial phenotype in all samples in both media; however, cell growths were delayed in the low‐Ca medium. In the high‐Ca medium, all the cultures had more unfastened cells and debris. Integrin b1, CK10, and p75 had no expression in all the primary cultures. p63 expression was registered in 39.2% and 34.7% (median, n = 3, ns) cells for EpiLife and DMEM/F12 media respectively. Expression of vimentin was found as very low in both media. ZO‐1 expression was calculated as 5.18 and 17.5 mkm (median, n = 3, ns) length per cells for EpiLife and media respectively.

Conclusions

It was confirmed that human labial mucosal epithelium could be cultured from a small biopsy without feeder cells in the culture media contained only three specific growth factors. Better cell morphology and lowered differentiation status were obtained in the 0.06Ca medium. Thus it was considered that the cell source, culture technique, and media formulations are suitable for autologous transplantation of cultured labial mucosal epithelium in patients with limbal stem cell deficiency.
Longitudinal changes in peripapillary retinal nerve fiber layer thickness in hypertension
Authors: Kim Jung Yeul
Published: December 2019

Purpose

To determine longitudinal changes in the peripapillary retinal nerve fiber layer (pRNFL) thickness in patients with hypertension (HTN).

Design

A prospective observational study.

Participants

Participants without any ophthalmic disease were divided into two groups: a HTN group (50 eyes) that included patients with HTN for ≥5 years and a control group.

Methods

After the initial visit, pRNFL thicknesses were measured four more times at 1‐year intervals using spectral‐domain optical coherence tomography. The pRNFL thickness was fitted using linear mixed models. Univariate and multivariate generalized linear mixed models were used to determine factors associated with pRNFL reductions over time.

Main Outcome Measures

The pRNFL thickness and rate of pRNFL thickness reduction.

Results

The mean ages of the HTN and control groups were 62.9 ± 6.2 and 60.7 ± 6.1 years, respectively, and they were not significantly different (P = 0.089). The baseline mean pRNFL thicknesses were 90.50 ± 8.31 and 93.90 ± 8.77 μm; they were significantly different (P = 0.049). The mean pRNFL reduction rate was −1.14 and −0.40 μm/year in the HTN and control groups, respectively; the interaction between group and duration was significant (P < 0.001). In the HTN group, all sectors showed a significant reduction over time, but in the control group, only the superior sector showed a significant reduction over time. In the linear mixed model determination of factors associated with pRNFL reduction, there was no significant factor in the control group. In the HTN group, age, and axial length showed significant results in both univariate and multivariate analyses (estimate: −0.43 and −3.59; P = 0.016 and 0.005, respectively).

Conclusions

Patients with HTN had a significantly greater decrease in pRNFL than normal individuals. Additionally, age and axial length significantly affected the reduction in pRNFL in HTN patients.
Longitudinal changes in the ganglion cell – inner plexus layer thickness in hypertension: A prospective observational study
Authors: Hyuk Lee Woo , Lim Hyung‐Bin , Shin Yong‐Il , Kim Jung‐Yeul
Published: December 2019

Purpose

To determine longitudinal changes in the ganglion cell‐inner plexus layer (GC‐IPL) thickness in patients with hypertension (HTN).

Design

A prospective observational study.

Participants

Participants without any ophthalmic disease and systemic except HTN were divided into two groups: a HTN group (49 eyes) and a control group (56 eyes).

Methods

After the initial visit, GC‐IPL thicknesses were measured four more times at 1‐year intervals using spectral‐domain optical coherence tomography. The GC‐IPL thickness was fitted using linear mixed models. Univariate and multivariate generalized linear mixed models were used to determine factors associated with GC‐IPL reductions over time.

Main outcome measures

The GC‐IPL thickness and redcution rate.

Results

The mean ages of the HTN and control groups were 60.3 ± 9.7 and 57.7 ± 7.9 years, respectively, and they were not significantly different (p = 0.137). The baseline average GC‐IPL thicknesses were 81.84 ± 6.67 and 84.86 ± 4.39 μm; they were significantly different (p = 0.008). The average GC‐IPL reduction rate was −0.64 and −0.19 μm/year in the HTN and control groups, respectively; the interaction between group and duration was significant (p < 0.001). In the HTN group, all sectors showed a significant reduction over time, but in the control group, the superior, inferior, inferonasal and superonasal sector showed a significant reduction over time. In the linear mixed model determination of factors associated with GC‐IPL reduction, there was no significant factor in the control group. In the HTN group, age showed significant results in both univariate and multivariate analyses (estimate: −0.24, p = 0.009). In minimum parameter age and mean IOP showed significant (estimate: −0.30 and −1.38, all p = 0.043)

Conclusions

Patients with HTN had a significantly reduction in GC‐IPL than normal individuals. Additionally, age and IOP affected the reduction in GC‐IPL in HTN patients.
Enhanced visualization of retinal vasculature using image processing
Authors: Jung Do‐Hyun , Taek Kim Yun
Published: December 2019

Objective

To develop a digital filter that enhances visualization of retinal blood vessels.

Methods

Four‐hundred 24‐bit color fundus images were analyzed and properties of red, green, and blue channels were extracted. Then, using hemoglobin absorption coefficients, the relevant weights for gray‐scale conversion that emphasizes retinal vessels were calculated. To evaluate images, edges were detected via convolution‐al 2D Laplacian kernel from the processed images, and the number of edges, number of effective edges, and sum of intensities of edges were evaluated. To validate the clinical usefulness, two independent observers graded 100 fundus photographs from subjects with diabetes mellitus before and after image process described above. Agreement between observers and the diagnosis from fluorescein angiography was calculated using Cohen’s kappa coefficient (κ).

Results

The values of weights for red, green, and blue channels were calculated to be −0.0572, 0.7335, and 2.2079, respectively. When comparing the images that were processed using the new digital filter based on these values with the original image, gray‐scale, green, red, blue, and green and blue digital filter images, the number of edges, effective edges, and sum of intensities of edges were all found to be significantly higher in the images processed with the new filter (p < 10−16). Cohen’s kappa coefficients (κ) of grading diabetic retinopathy from two independent observers comparing to the diagnosis from fluorescein angiography were 0.36, 0.29 respectively from fundus photographs and 0.61, 0.65 respectively from processed images. And Cohen’s kappa coefficients (κ) on the presence of any grade of diabetic retinopathy from two independent observers comparing to the diagnosis from fluorescein angiography were 0.69, 0.69 respectively from fundus photographs and 0.86, 0.84 respectively from processed images.

Conclusions

The RGB filter developed here was based on actual fundus images. The hemo‐globin absorbance reinforced the edges of retinal blood vessels, verifying that the new RGB filter can en‐hance the visualization of retinal vasculature. Significance: This digital filter was developed targeting hemoglobin for enhancement of retinal vasculature. Because this digital filter is simple to build, it can be applied for fundus camera.
Clinical & pathologic features of lacrimal ductal cyst
Authors: Choi Hye Sun , Jang Jae Woo , Kim Sung Joo , Baek Ji Sun
Published: December 2019

Purpose

To evaluate the clinicopathological features of lacrimal ductal cyst.

Methods

A retrospective study was performed on patients who underwent the surgery to remove the lacrimal ductal cyst at Kim’s Eye Hospital from January 2013 to December 2017. We analyzed the clinical data obtained from the medical records, including slit lamp examination and pathologic findings.

Results

57 patients was enrolled in this study. There was a male predominance and the average age was 42.9 years (range 15–73). 55 patients showed unilateral disease and two patients showed bilateral disease. Palpable mass lesion was most common symptom, but other symptoms, such as discharge, injection, cystic lesion, itching, epiphora, pain, swelling, foreign body sensation were also seen. Conjunctival injection was most common findings in the slit lamp examination. Pathologically, acute and chronic inflammation was most common findings. Cilia was founded on the cyst in 45.6% and concretion was founded on the cyst in 42.1% in pathologic examination.

Conclusions

Lacrimal ductal cyst is rare and few case series were reported. Large population study of lacrimal ductal cyst was first. This report would be helpful to distinguish the lacrimal ductal cyst from other disease in lateral canthal area.
Primary Open Angle Glaucoma and Vascular Risk Factors: a review of population based studies from 1990 to 2017
Authors: Grzybowski Andrzej , Och Mariusz , Kanclerz Piotr , Leffler Christopher
Published: December 2019

Purpose

Glaucoma is one of the leading causes of blindness worldwide, and as the proportion of those over age 40 increases, so will the prevalence of glaucoma. The pathogenesis of primary open angle glaucoma (POAG) is unclear and multiple ocular risk factors have been proposed, including intraocular pressure, ocular perfusion pressure, ocular blood flow, myopia, central corneal thickness, and disc hemorrhages. The purpose of this review was to analyse the correlation between systemic vascular risk factors and POAG pathogenesis based on major epidemiological studies.

Methodology

We used the PubMed database to identify studies including the term glaucoma in association with the following keywords: vascular risk factors, systemic risk factors, blood pressure, systemic hypertension, systemic hypotension, diabetes, dipping, vasospasm, age and migraine.

Results

The search identified 270 unique articles. After including only relevant English‐language articles only 66 studies were reported in the analysis. Reports presenting the association between POAG and systemic vascular risk factors included a total of over 50,000 patients. Several epidemiological studies confirmed the importance of vascular risk factors in the pathogenesis and progression of glaucomatous optic neuropathy, including hypertension, blood pressure dipping. The pooled analysis confirmed hypertension as the most significant risk factor for primary open angle glaucoma.

Conclusions

Vascular risk factors play a significant role in the pathogenesis and progression of glaucoma. The association between POAG and diabetes mellitus type 2 or migraine still needs to be evaluated in future studies.
The effect of antiamoebic agents and Ce6‐PDT on acanthamoeba castellani trophozoites and cysts, in vitro
Authors: Shi Lei , Stachon Tanja , Latta Lorenz , Ibrahem Elhawy Mohamed , Gunaratnam Gubesh , Orosz Erika , Kiderlen Albrecht F. , Seitz Berthold , Bischoff Markus , Szentmáry Nóra
Published: December 2019

Purpose

To analyze the concentration dependent effect of diamidines (hexamidine‐diisethionat (HD), propamidin‐isethionate (PD), dibromopropamidine‐diisethionat (DD)); biguanides (polyhexamethylen biguanid (PHMB), chlorhexidine (CH)); natamycin (NM); miltefosine (MF); povidone iodine (PVPI) and chlorin e6 photodynamic therapy (PDT) on Acanthamoeba castellani trophozoites and cysts, in vitro.

Methods

Acanthamoeba castellani strain was cultured in 712 peptone‐yeast extract‐glucose (PYG) medium. Thereafter, trophozoites or cysts were cultured in 0.25–0.1% HD, PD or DD, or 0.005–0.02% PHMB, CH or NM or 0.001625–0.0065 MF or 0.25–1% PVPI containing PYG medium for 2 h or underwent Chlorin e6‐PDT. Then, the percentage of dead trophozoites was determined by CytoTox 96® Non‐Radioactive Cytotoxicity assay and trypan blue staining and those of cysts using trypan blue staining. Treated trophozoites and cysts were also inoculated to non‐nutrient agar Eshericia coli plates and were observed for 5 weeks.

Results

All concentrations of different antiamoebic agents had a significant cytotoxic effect on AK trophozoites and cysts (p < 0.05), except 0.02% PHMB and CH, using trypan blue assay for trophozoites, and Ce6‐PDT for cysts. Observing the agar plates, HD, PD, PHMB, CH, NM and PVPI led to morphological changes of acanthamoeba trophozoites, which could not form cysts within 5 weeks. DD and MF treated cysts could excyst and later encyst again.

Conclusions

Conservative treatment using different antiamoebic agents or Ce6‐PDT can not eradicate all Acanthamoeba castellani trophozoites and cysts. In vitro analyzis of treatment efficacy of different antiamoebic agents may alow a more specific treatment in acanthamoeba keratitis.
Required stage dependent therapy in coats disease
Authors: Brockmann Claudia , Müller Bert , Schönfeld Shideh , Winterhalter Sibylle , Zeitz Oliver , Joussen Antonia M.
Published: December 2019

Purposes

Coats disease is a rare retinal vascular disorder characterized by telangiectasia and exudation affecting predominantly young male. Due to its rareness, analyses of large cohorts over long periods are of particular importance to give a prognosis for the usually very young patients and their parents, especially with regard to required therapy.

Methods

We retrospectively analyzed patients diagnosed with Coats disease and treated between May 1992 und March 2019. The minimum follow‐up was 12 months. We evaluated the interventional procedures with regard to the initial stage.

Results

Seventy‐seven eyes of 75 patients were included in the analyses. Eighty‐one percent were male; mean age was 17.8 ± 18.2 years (range 1–71; median 10.0). Mean follow‐up time was 7.3 ± 5.6 years (range 1.1–21.4; median 6.5). In eyes with stage 1 (n = 2) only lasercoagulation (LC) was necessary. In stage 2A 65% (11/17) of eyes required LC, 30% (5/17) cryotherapie (CT), 25% (4/17) vitrectomy (VT) and 18% (3/17) ruthenium brachytherapy (RT) due to secondary vasoproliferative retinal tumor. In stage 2B 88% (29/33) were treated with LC, 30% (10/33) with CT, 21% (7/33) needed VT and 6% (2/33) RT. In 89% (8/9) of eyes staged 3A1 LC was necessary, in 100% (9/9) CT and in 44% (4/9) VT. Three eyes were staged 3A2 and all of them required VT, two additional LC and one additional CT. Similar results were seen in stage 3B (five eyes): in all eyes VT was performed, in 80% (4/5) LC and CT was done in addition. Four of six (66%) stage 4 eyes were enucleated, the 2 remaining received CT and VT or RT. We had 2 stage 5 eyes, thereof one required enucleation.

Conclusion

Therapy in patients with Coats’ disease strongly depends on the initial stage with less intense procedures in early stages. While most invasive treatment was necessary in stage 3, the rate of enucleation was, as expected, highest in stage 4. Therefore early diagnosis and immediate treatment is of highest priority to preserve the eye.
Efficacy and safety of Resvega in diabetic macular edema: preliminary results of a pilot study
Authors: Chatziralli Irini , Dimitriou Eleni , Chatzirallis Alexandros , Aissopou Evaggelia , Theodossiadis Panagiotis
Published: December 2019

Purpose

The protective effects of resveratrol within the eye are extensive. It has been demonstrated to have anti‐oxidant, anti‐apoptotic, anti‐tumourogenic, anti‐inflammatory, anti‐angiogenic and vasorelaxant properties. Of note, resveratrol inhibits vascular endothelial growth factor (VEGF) expression in human adult retinal pigment epithelium cells. The purpose of this study was to examine the efficacy and safety of vitamin supplements with resveratrol (Resvega, Thea Laboratories) in patients with diabetic macular edema (DME).

Methods

Participants in this prospective, pilot study were 23 patients with DME, who were previously treated with anti‐VEGF injections. All patients presented mild DME, with good visual acuity (>7/10) and central retinal thickness (CRT) 280–330 μm, where anti‐VEGF injection was not needed at the current time at the discretion of the physician. All participants received Resvega (2 tablets once/day) for 4 months. Visual acuity and CRT were assessed every month, while potential adverse events were recorded.

Results

The visual acuity remained stable at the 4‐month follow‐up. The mean CRT increased slightly at month 4 post initiation of treatment compared to baseline, but the difference was not statistically significant. Four out of 23 patients (17.4%) needed additional anti‐VEGF injection at the end of the follow‐up due to worsening of macular edema. No adverse events were reported.

Conclusions

Resvega was found to be safe and effective in patients with DME, since it stabilized visual acuity and CRT in the short‐term follow‐up of 4 months. Long‐term studies are needed to confirm our results.
Outcome simultaneous replacement of stromal donor lenticul in cornea with ectasia during Smile surgery
Authors: Doroodar Farideh
Published: December 2019

Purpose

Lenticule implantation can be used to correct vision problems. The aim of the present study was to investigate the feasibility and effects of Simultaneous replacement of stromal donor lenticul in cornea with ectasia during Smile surgery

Methods

Six patients with decreased visual acuity due to corneal ectasia were included in this prospective pilot study. These lenticules were extracted during SMILE procedures using the VisuMax femtosecond laser (Carl Zeiss Meditec) on 6 donors with myopia and Simultaneous replacement of stromal donor lenticul in cornea with ectasia. Pre‐ and postoperative (1 or 3 days, 1 month, and 6 months) slit lamp microscopy, corneal topography, anterior segment optical coherence tomography, and in vivo confocal microscopy were performed.

Results

The surgeries and postoperative follow‐up examinations were uneventful and no complications were noted over 6 months of follow‐up. At the last measurement, the corrected distance visual acu‐ity of all recipient eyes gained at least two lines. Two eyes (33.3%) gained at least two lines of uncorrected distance visual acuity compared to their preoperative levels.Mean keratometric power increased by 5.97 ± 3.73 diopters and central corneal thickness increased by 55.25 ± 36.38 μm. Anterior segment optical coherence tomography observation showed the lenticule was transparent with a visible demarcation line during the follow‐up examination.

Conclusions

This technique seems to be feasible and safe for increasing corneal stromal thickness and changing corneal refractive power, which may provide a useful method for treatment of keratoectasia, presbyopia, and hyperopia.
NRF‐2 and PGC‐1α signaling regulate epithelial‐mesenchymal transition in mouse model
Authors: Felszeghy Szabolcs , Ruuth Johanna , Viiri Johanna , Hyttinen Juha , Koskela Ali , Kaarniranta Kai
Published: December 2019

Purpose

Epithelial‐mesenchymal transition (EMT) is estimated to play critical role in the development of advanced age‐related macular degeneration (AMD). Key players associated with EMT were studied in NRF‐2 and PGC‐1α knock‐out mice model resembling dry AMD phenotype.

Methods

Retina paraffin sections from NRF‐2 and PGC‐1α knock‐out mice and wild‐type (WT) animals were analyzed for EMT biomarkers by semiquantitative confocal, highly specific and sensitive immunofluorescence method. Retinal pigment epithelium (RPE) cell morphology was analyzed by optical coherent tomography and ultrathin transmission electron microscopy.

Results

Semiquantitative image analysis revealed that collagen 1 is downregulated in knock‐out samples compared to WT animals. Upregulation of key EMT markers such as, vimentin, e/n‐cadherins, snail, fibronectin and slug were detected in the knock‐out mice rather than in WT samples. RPE cells showed morphological transition in the knock‐out animals.

Conclusions

Disturbed anti‐oxidant production through nrf‐2 and mitochondrial biogenesis through pgc‐1α seem to regulate emt in the dry amd resembling mouse model.
Fluocinolone acetonide for the treatment of chronic diabetic macular edema: an Italian real‐world experience
Authors: Zollet Piero , Capone Luigi , Lattanzio Rosangela , Bandello Francesco
Published: December 2019

Purpose

This is a retrospective real‐world study on the use of Fluocinolone acetonide (FAc) intravitreal implant (Iluvien®) for the treatment of chronic diabetic macular edema (DME) insufficiently responsive to available therapies. Its aim is to give a further contribution in assessment of efficacy and safety of this drug delivery system.

Methods

Patients included were collected from July 2017 to May 2019. 53 pseudophakic chronic DME patients (69 eyes) were enrolled to evaluate anatomo‐functional outcomes; namely, best corrected visual acuity (BCVA), central macular thickness (CMT) and complications (i.e. rise in intraocular pressure (IOP) and need for IOP lowering medications, hemovitreous, endophtalmitis) of Iluvien® implants. The study partecipants were all previously unsuccessfully treated with first‐line therapies (anti‐VEGF and laser) and intravitreal dexamethasone (Ozurdex®). Patients were considered eligible only in presence of response to the latter drug without significant intra‐ocular pressure increase. Information about further need for DME additional therapies post‐FAc were also recorded. The data of 18 eyes with at least 12 months follow‐up are reported.

Results

At baseline the mean overall BCVA was 58.3±17.5 ETDRS scale letters. Post‐FAc implant, mean BCVA rised to 63.9 ± 15.2, 60.8 ± 18.3, 61.3 ± 16.9 and 64.5 ± 13.9 ETDRS letters at 2, 4, 6 and 12 months respectively. The percentage of eyes achieving 15 or more ETDRS letters improvement within 12 months was 33.3%. CMT values, from a baseline mean of 517.4 ± 204.0 µm, decreased to 364.9 ± 138.4 µm, 410.8 ± 192.4 µm, 339.0 ± 126.8 µm and 339.9 ± 82.0 at 2, 4, 6 and 12 months, respectively. In this period of observation a dry macula (<300 µm) was obtained in 33.3% of eyes. Recorded complications included increase in IOP with need for IOP lowering medications in 18.9% of study population. Only 8.7% patients needed to perform additional DME therapies for poor response to FAc.

Conclusions

The preliminary results of our study support the use of FAc for the treatment of chronic DME. Efficacy and safety profiles seem to be comparable with the ones of the FAME pivotal study but with less IOP concerns. Selecting patients previously treated with intravitreal steroids and without increase in IOP can further minimize risks. Mean increase of IOP over time can be safely managed with topical therapy in the large majority of cases.
Observational study of magnitude of ocular manifestations of rheumatoid arthritis in a tertiary care hospital in East India
Authors: Dutta Udbuddha
Published: December 2019

Purpose

To evaluate the magnitude of ocular manifestations in patients suffering from rheumatoid arthritis. To establish a statistical significance of age of patients to frequency of ocular manifestations. To establish a statistical significance of duration of disease to frequency of ocular manifestations.

Methods

Study Design: Cross sectional observational study. Sample Size: 144. Duration of Study: 18 months. Case control was not required in this study. Investigations: Slit lamp biomicroscopy with 90 D Volk lens was done for anterior and posterior segment examination. Gonioscopy, Applanation Tonometry, Automated Perimetry and Indirect Ophthalmoscopy were done . Dry eye evaluation was done. Statistical Analysis: SPSS version 20 was used with a p value of less than 0.05 taken as significant.

Results

Out of 144 patients, females (118) dominated .Ocular manifestations were seen in 53(36.8%) patients, bilateral in 35 (66%) patients and multiple in 32 (60.4%) patients. Dry eye was the most common ocular manifestation (30.5%). The duration of disease was statistically significant(p=0.001)with respect to ocular manifestations and also age groups (p = 0.000).

Conclusion

Dry eye was the most common ocular manifestation. The duration of disease was statistically significant with respect to ocular manifestations. The duration of disease was statistically significant when co related with age groups.
Clinical stability in the fellow non‐operated eye from asymmetric keratoconus patients
Authors: Lopes Diogo , Baptista Pedro , Sena Nelson , Barros Sandra , Machado Inês , Ambrósio Renato
Published: December 2019

Purpose

To assess the clinical status of corneal ectasia, including clinical outcomes and tomographic/biomechanical assessments of asymmetric keratoconus patients who had surgical treatment only in the most advanced eye.

Methods

This retrospective study included 100 eyes of 50 asymmetric keratoconus patients who had surgery in one eye. The eyes were divided in two groups, the operated group (OG) which underwent surgery and the fellow non‐operated eyes (NOG). Both groups received medical treatment for ocular allergic disease and ocular surface optimization, along with the general advice to avoid eye rubbing.

Results

Mean follow‐up time was 41 ± 33.26 months (range 6.4–182.4) and mean age at the first visit was 25 ± 9.8 years (range 6–60), including 43 patients with less than 34 years. Regarding to the NOG, the baseline average UDVA was 0.40 (20/50) ± 0.46 logMAR and CDVA was 0.10 (20/25) ± 0.17 logMAR. In the last visit, despite of no surgical treatment, average UDVA and CDVA showed improvement to 0.34 (20/44) ± 0.43 (p > 0.05) and 0.06 (20/23) ± 0.15 logMAR (p = 0.02), respectively. Analysis of biomechanical parameters of the NOG showed a statistically significant difference (p < 0.05) of deflection amplitude ratio. The comparison of ABC parameters of Belin’s tomographic grading system between first and last visit showed non statistically significant difference (p > 0.05) in the NOG.

Conclusion

Clinical anti‐allergic and ocular surface optimization treatment, along with patient education for avoiding eye rubbing (as in the Violet June Keratoconus Awarenes Campaign) is indicated to all keratoconus/ectasia patients best first line of treatment. The stability of the ABCD parameters of Belin grading system in the NOG and even the improvement of CDVA supports that, regardless age, in many cases with mild ectasia, medical management is sufficient without the need for surgical procedure, even in young patients.
The effect of Tetrahydrocannabinol on optic nerve head blood flow in healthy subjects
Authors: Hommer Nikolaus , Kallab Martin , Szegedi Stephan , Puchner Stefan , Bauer Martin , Werkmeister René , Schmetterer Leopold , Abensperg‐Traun Marihan , Garhöfer Gerhard , Schmidl Doreen
Published: December 2019

Purpose

There is ample evidence that optic nerve head blood flow (ONHBF) is impaired in patients with glaucoma. Tetrahydrocannabinol (THC) is used in the treatment for glaucoma in some countries for several years due to its intraocular pressure (IOP) lowering effect. Beside its IOP lowering potential, THC features neuroprotective effects and may improve ocular hemodynamics. The aim of the present study was to investigate whether oral administration of THC alters ONHBF in healthy subjects.

Methods

The present study was carried out in a double‐masked, randomized, placebo‐controlled, two‐way crossover design in 24 healthy subjects. For each study participant, two study days were scheduled, on which they either received capsules containing 5 mg Dronabinol (a synthetic THC) or placebo capsules identical in appearance. ONHBF was assessed using laser Doppler flowmetry at baseline and 1 hr after drug administration. Ocular perfusion pressure (OPP) was calculated as 2/3*mean arterial pressure (MAP) ‐ IOP.

Results

Twenty‐four healthy subjects (12 female and 12 male) aged between 20 and 35 years participated in the present study. The study medication was well tolerated and no cannabinoid‐related psychoactive effect was observed. Neither administration of THC nor placebo had an effect on IOP, MAP or OPP. In contrast, THC significantly increased ONHBF by 9.5 ± 8.1% whereas placebo did not show a change in ONHBF (0.3 ± 7.4 % vs. baseline, p < 0.001 between groups).

Conclusions

The present data indicate that orally administered, low dose THC increases ONHBF in healthy subjects without affecting IOP, OPP or inducing psychoactive side effects. Further studies are needed to investigate whether this effect can also be observed in patients with glaucoma.
Mantle cell lymphoma: how not to be misled
Authors: Schümmer Laura , Ninclaus Virginie , Callebert Ineke , Lantsoght Helena , Geldhof Kurt , Vermeersch Hubert , De Schryver Ilse
Published: December 2019

Purpose

To report a case of a multifocal mantle cell lymphoma (MCL) affecting both nodal and extra nodal sites in the orbital and maxillofacial region.

Methods

Observational report of a patient presenting with palpebral masses in both upper eyelids and salivary glands. The patient underwent an extensive multidisciplinary work‐up including MRI, F 18 FDG PET/CT and biopsy with morphological and immunohistochemical analysis.

Results

A 77‐year‐old Caucasian male presented with asymmetrical painless swelling in both upper eyelids for more than 6 months. He reported weight loss but no fever or night sweats. His medical history included a JAK 2 + myeloproliferative disorder. He had no decreased vision and ocular examination was normal. Palpation of the head and neck revealed a swelling of the parotid and submandibular glands as well as a cervical lymphadenopathy. MRI confirmed multifocal lesions in the orbital and maxillofacial region. AS PET/CT scan showed a pathological FDG uptake at both upper eyelids with sparing of the lacrimal glands, the presumed diagnosis of a stage IV lymphoma was withheld. Incisional biopsies of the upper eyelid and supraclavicular node were performed.Immunohistochemical analysis were positive for CD20, CD5, Cyclin D1, Bcl‐2 but negative for CD10 and Bcl‐6. High expression of the proliferation index by Ki‐67 (locally up to 50%) was observed.

Conclusions

The purpose of this case was to describe an uncommon presentation of a non‐Hodgkin lymphoma. The diagnosis of MCL was based on a biopsy with immunohistochemical analysis. Although MCL is relatively uncommon, ophthalmologists should be aware of this rare diagnosis.
3D morphometric study of the nasolacrimal duct and its implication in recanalization of nasolacrimal duct obstruction
Authors: Lee Sohyun , Lee U‐Young , Lee Won‐Joon , Kim Dong‐Ho , Seok Nam Yong , Kim In‐Beom , Kim Yi‐Suk
Published: December 2019

Purposes

The nasolacrimal recanalization, consisting of retrograde removal of obstructing tissues using electrocauterization, is an evolutionally developed surgical procedure to treat the nasolacrimal duct (NLD) obstruction. To perform the nasolacrimal recanalization requires an understanding of three‐dimensional (3D) structure of the NLD, but very few data are available about its stereotactic shape. This study aims at investigating the anatomy of the NLD through 3D visualization and metric assessment of 3D models obtained from the cranial CT‐scans.

Methods

This study included 20 males and 20 females (range: 18–68 years), who underwent autopsy at the National Forensic Service Seoul Institute, Seoul, Korea. Post‐mortem cranial CT‐scans were achieved in helical mode with slice thickness of 0.75 mm and 120 kV. 3D models of the NLD were reconstructed from serial CT slices after performing semi‐automated segmentation by tracing and filling the outline of the nasolacrimal duct by Mimics software (version 20.0, Materialise, Leuven, Belgium).

Results

Overall length of NLD, anteroposterior and transverse entrance diameters of bony NLD (BNLD), and lacrimal sac‐BNLD angle was significantly higher in males than females. Compared with right and left, most variables showed no significant differences in statistics, except for lacrimal sac‐BNLD angle. BNLD orientation type in coronal plane showed outward type than inward by over 80%. Collectively, the whole appearance of the NLD was shaped like a bowleg in which the distal part is relatively turned inward.

Conclusion

These results suggest that 3D models of the NLD were crucial for understanding structural recognition, mainly related to model‐based image analysis, and useful to aid in the surgical procedure and treatment of the nasolacrimal duct obstruction.

The authors wish to acknowledge the financial support of the Catholic Medical Center Research Foundation made in the program year of 2019 (No. 552019B000100003).
Genetic analysis of pseudoexfoliation glaucoma risk in an Irish population
Authors: Eivers Sarah , Greene Alison , Dervan Edward , O’ Brien Colm , Wallace Deborah
Published: December 2019

Purpose

Glaucoma is an optic neuropathy and a leading cause of irreversible blindness worldwide. Although there are many factors that may contribute to disease predisposition, severity and progression, pseudoexfoliation (PXF) syndrome represents a significant cause for developing open angle glaucoma. Single nucleotide polymorphisms (SNPs) within the lysyl oxidase like (LOXL) 1 gene have been identified as a major risk factor for PXF syndrome and PXF glaucoma (PXFG), specifically SNPs within the exon 1 and intron 1 regions of the gene. The common haplotype (G‐G) of 2 SNPs within exon 1, rs1048661 and rs3825942, are the strongest associated risk factor for PXF in Caucasian populations. However this risk haplotype is switched in some populations. Herein, a study was undertaken to genotype an Irish population for PXF risk‐associated SNPs within the LOXL1 gene.

Methods

Patient cohorts of PXFG, PXF and cataract controls were recruited following informed consent. Patients from each cohort were then genotyped for the 2 high risk associated SNPs within exon 1 (rs1048661 and rs3825942), along with 3 SNPs within intron 1 (rs1550437, rs6495085 and rs6495086) of the LOXL1 gene.

Results

The high risk haplotype (G‐G) was most prevalent in PXFG patients compared to control patients. The low risk (G‐A) haplotype was only seen in control patients. Additionally, genotypes of several SNPs within intron 1 were also found to be present at higher frequencies within the PXFG/PXF patient cohort compared to control patients.

Conclusion

Collectively, these results represent the first study to genotype PXF‐associated SNPs within LOXL1 in an Irish population and aids in our understanding of the genetic component of developing PXF and PXFG.
Nanofibrous membranes reveal better properties for culturing of RPE cells in comparison with commercial scaffolds
Authors: Ardan Taras , Zemanova Lucie , Ellederova Zdenka , Drutovič Saskia , Studenovská Hana , Popelka Stepan , Kepkova‐Vodickova Katerina , Rohiwal Sonali , Sedlackova Miroslava , Motlik Jan
Published: December 2019

Purpose

Malfunction of the retinal pigment epithelium (RPE) is a cause of the whole row of retinal degenerative diseases such as age related macular degeneration (AMD). RPE replacement based on transplantation of cultured RPE cells on artificial membranes into the retina can be a perspective way for the therapy of these incurable diseases.

Methods

Porcine primary RPE cells were isolated from cadaverous porcine eyes on two types of artificial membranes: commercial polyester scaffolds Transwell and polylactate nanofibrous membrane manufactured by us. Both membranes have the same pore sizes. For the detection of important functional and morphological markers of RPE cells, we used three types of assays ‐ immunocytochemistry, real‐time qPCR and electron microscopy. The ultrastructure of cultured RPE cells was examined by scanning and transmission electron microscopy (EM).

Results

Using real‐time qPCR assay, we found that cultured cells on nanofibrous membranes demonstrated higher expressions of mRNAs typical for RPE cells. Moreover, immunocytochemical detection of cultured cells on nanomembranes revealed more intensive staining of all important markers in comparison with commercial ones. Electron microscopy of both membranes confirmed a confluent layer of RPE cells and their correct morphological structure, which was comparable with the cells of native RPE. Only on nanofibrous scaffolds and using scanning EM we found the better development of RPE cilia.

Conclusion

Our results enable us to conclude that RPE culturing on nanomembranes improved the final quality of RPE cells by better maturation and long‐term survival of RPE monolayer in contrary with culturing on commercial scaffolds. Such cultured RPE cells are fully able to replace non‐functioning native RPE cells during cell therapy.
Apparent fiber density of glaucomatous optic nerves
Authors: Haykal Shereif , Jansonius Nomdo , Cornelissen Frans
Published: December 2019

Purpose

To investigate alteration of apparent fiber density (AFD), a novel diffusion MRI (dMRI) measure of white matter degeneration, in the optic nerves (ONs) of glaucoma patients. Furthermore, we aimed to study the correlation between AFD of glaucomatous ONs and peripapillary retinal never fiber layer (pRNFL) thickness and visual field mean deviation (VFMD), in order to assess the viability of AFD as a possible alternative measure for diagnosing and monitoring glaucoma.

Methods

Cross‐sectional study of 15 glaucoma patients and 15 healthy participants. Subjects underwent dMRI scans while being asked to close their eyes and keep eye motion to a minimum. An average population template was produced from the dMRI scans of all the subjects, and probabilistic tractography was then used to track the ONs in template space. Average track AFD was calculated for a single randomly selected ON for each subject. pRNFL thickness and VFMD measurements were acquired using optical coherence tomography and standard automated perimetry, respectively. Average AFD of glaucomatous and normal ONs were compared using ANCOVA, correcting for age as a nuisance covariate, and the correlation between average AFD of glaucomatous ONs and their corresponding pRNFL thickness and VFMD was tested using Spearman’s rank correlation test.

Results

Glaucomatous ONs showed a significantly lower AFD compared to healthy ONs (0.123 ± 0.034 versus 0.212 ± 0.027 a.u., respectively; p < 0.01). Average AFD of glaucomatous ONs showed a strong positive correlation with average pRNFL thickness (r = 0.863, p < 0.01) and VFMD (r = 0.850, p < 0.01).

Conclusions

The ONs of glaucoma patients exhibit a significant loss of AFD, which correlates strongly with both pRNFL thinning and visual field loss. Therefore, measuring ON AFD in glaucoma patients could potentially be an alternative to other established clinical measures, which could prove to be beneficial to patients who are not ideal candidates for certain clinical tests.
Influence of mitochondrial haplogroups in response to ranibizumab teraphy in neovascular age‐related macular degeneration
Authors: Esteban Olivia , Javier Ascaso F. , Lopez Isabel , Marco Sara , Montes Paula , Karlsruher Gisela , Ruiz‐Pesini Eduardo
Published: December 2019

Purpose

To analyze the results after one year with intravitreal ranibizumab therapy in neovascular Aged‐related macular degeneration (nAMD) patients according to the mitochondrial‐DNA haplogroup (mt‐DNA Hg)

Methods

Ninety‐eight eyes corresponding to 91 Caucasian patients with nAMD were treated with an initial series of 3 monthly loading intravitreal ranibizumbab injections 0.5 mg in 0.05 ml followed by a flexible pro re nata (PRN). Patients were classified into four groups according to their mtDNA genetic background determined by PCR (Hg H‐ m.7028C>T; Hg HV‐ m.14766T>C; Hg JT‐ m.421 6T>C; and Hg U‐ m.12308A>G). Statistical tests (chi‐square, Kolmogorov–Smirnov, paired and unpaired t test, ANOVA, Mann–Whitney U, Kruskal–Wallis H, Wilcoxon and Friedman tests). A p value < 0.05 was considered to be statistically significant.

Results

Gender, age and risk factors were equally distributed among the four groups. There were no significant differences between groups in baseline best corrected visual acuity (BCVA), central foveal thickness (CFT) and neovascular lesion type. After three loading dose, BCVA and CFT was significantly higher in all Hg without differences between them. Eighteen patients were not included at 12 months because of exclusion criteria. After receiving in average 6.7 ± 1.7 inyections of ranibizumab at 12 month, BCVA and CFT remained stable in haplogroups HV and U without significant worsening; however, haplogroup JT showed lower BCVA and higher CFT values than baseline (p = 1.00). In fact, CFT values were significantly different between groups (p = 0.004, Kruskal–Wallis H test) at 12 month. In particular, haplogroups JT and U were significantly different between them (p = 0.010, multiple comparison tests).

Conclusions

mtDNA genetic background showed different response to intravitreal ranibizumab therapy at 12 month. It could be a potencial biomarker to predict the response to intravitreal ranibizumab therapy in nAMD patients.
Changes in the expression of autophagy markers in a rat model of retinopathy of prematurity
Authors: Anna Pesce Noemi , Locri Filippo , Dal Monte Massimo , Andrè Helder
Published: December 2019

Purpose

Autophagy is an essential process in maintaining the normal cellular homeostasis and energy balance under physiological conditions. In retinal diseases, autophagy helps retinal cells defend themselves against harmful stress; however, excessive autophagy may result in retinal deterioration. Modulating autophagy may provide an alternative therapeutic strategy to treat retinal diseases. Retinopathy of prematurity (ROP) is a human vascular disease characterized by the formation of neovascularization in the premature newborn retina. There is only limited information on the role of autophagy in ROP.

Methods

A rat model of oxygen‐induced retinopathy (OIR), an acknowledged model of ROP, was used to evaluate changes in the expression of key mediators of autophagy induced by the disease. In this model, rat pups are exposed to alternating cycles of 50% and 10% oxygen for 24‐h for the first 14 days followed by exposure to the room air until post‐natal day 18. The expression of autophagy markers from birth to post‐natal day 18 was assessed at transcript and protein levels by real‐time PCR and Western blot, respectively. In addition, the phosphorylation status of signaling molecules known to activate or to repress autophagy was investigated.

Results

In control rats, the autophagic flux decreased over time during post‐natal development. In contrast, in OIR rats the levels of autophagic markers transiently increased at post‐natal day 7 to then gradually decrease until post‐natal day 18.

Conclusions

The present findings sustain the role of dysregulated autophagic processes in the pathogenesis of ROP and point to the targeting of autophagy as a potential treatment for neovascular eye diseases.