bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular diagnostics and ophthalmic pathology: Where are we up to?
Authors: Coupland Sarah
Published: December 2019

Surgical pathology is rapidly developing and evolving, with the incorporation of new technologies, which enable the pathologist to provide more accurate diagnoses as well as additional information that is important for treatment choices, response prediction and prognostication. The newer technologies encompass molecular pathology, digital pathology, as well as artificial intelligence, and can be applied on both tissue and liquid samples. Molecular pathology includes the application of a wide range of ‘omics – i.e. genomics, transcriptomics, proteomics, metabolomics etc. Multicentre collaborations have enabled the sequencing of the human genome, the development of the human protein atlas and the human metabolome database. These projects provide the basis of designing new molecular panels and tests to be used in routine pathology. In this lecture, I will take you through how molecular diagnostics have fast‐tracked ophthalmic pathology into an exciting new era of improved personalised medicine, and have enabled a better understanding of the pathogenesis of eye diseases – particularly eye tumours – and this, in turn, has allowed for the development of targeted treatments.
Dealing with the complication of uveitis
Authors: Tranos Paris
Published: December 2019

Uveitis is a relatively rare but potentially sight threatening condition affecting usually patients at working age. It is considered an ophthalmic emergency requiring thorough examination and urgent treatment to control the inflammation and manage associated ocular complications. Identifying the underlying etiology is often challenging since many inflammatory conditions share common features with overlapping characteristics. A systematic approach during clinical examination, with effective interpretation of clinical signs and imaging results is essential in order to reveal the correct diagnosis. An update in current imaging trends for inflammatory disorders along with pearls in optimal diagnostic techniques will be presented through a plethora of relevant clinical cases.
Co‐delivery of neuroprotective agents from biodegradable microspheres
Authors: Rocio Herrero‐Vanrell
Published: December 2019

Glaucoma is considered a group of chronic eye diseases with multifactorial etiology. In this neurodegenerative disease, blindness is associated with damage to the optic nerve and retina with non‐reversible degeneration of retinal ganglion cells (RGCs). Several glaucomatous patients undergo intraocular pressure (IOP) elevation and hypotensive agents are useful to return the IOP to normal values. However, glaucoma may progress despite IOP‐lowering treatments and neurodegeneration is still present in the patients affected. Neuroprotective therapies can be defined as pharmacological treatments related to the preservation of neuronal integrity. Because of the multifactorial and chronic characteristics of glaucoma, the applicability of neuroprotective therapies involves the use of long term combined treatments. As neuroprotection of RGCs can be approached from different pathways, co‐delivery of neuroprotective active substances emerged as a therapeutic strategy thanks to the use of PLGA microparticulate drug delivery systems. Contrary to larger devices, PLGA microspheres can be injected in the vitreous as an aqueous suspension through standard needles (27‐34 G). As PLGA is a biodegradable polymer, particles gradually disappear from the site of injection and it is not necessary to surgically eliminate them from the vitreous once the active compounds have been released.
Retinal imaging – a window into brain mechanisms
Authors: Castelo Branco Miguel
Published: December 2019

The retina is increasingly being recognized as a window to brain neurodevelopment, ageing and degeneration. This non‐invasive window to vascular and neural function has shown promise to modify disease diagnosis, follow‐up and management. Here we review imaging evidence reflecting critical interactions between ageing, systemic disorders (diabetes) and neurodegenerative diseases. We will also address neural and vascular compartments and their critical interfaces, blood‐retinal and blood‐brain barriers. It remains to be clarified how brain neuroinflammation and amyloid deposition can be mirrored by surrogate markers at the level of the retina. We also address the intriguing link with diabetes as a systemic disease where all these factors are important in relation to barrier function and neurodegeneration associated with normal/pathological ageing. The association between abnormal retina and brain development will also be discussed, in relation to imaging approaches using the retina as a window into the brain.
Beyond our vision: Ultrastructural lesson from the analysis of PGC1‐α/Nrf‐2 compound null mutant mice retina
Authors: Felszeghy Szabolcs
Published: December 2019

The retinal pigment epithelium (RPE) and photoreceptors are degenerated in age‐related macular degeneration (AMD). Although the mouse has no macula similar degenerative signs can be observed in mouse compared with human tissue. Thus, ultrastructural studies of mouse AMD models are important to understand more accurately the pathologic AMD events. Using our new dry AMD mouse model, we examined at ultrastructural level the influence of genetic deficiency of PGC1‐α/Nrf‐2 on the PINK1 (PTEN‐induced kinase 1) and PARKIN (E3 ubiquitin ligase) expression pattern by using confocal, electron and immunoelectronmicroscopy. Benefits and challenges in these techniques are discussed to provide important clues about AMD ultrastructural pathogenesis.
Recognising uveitis emergencies – how to avoid pitfalls
Authors: James Teifi
Published: December 2019

True emergencies are uncommon in uveitis patients. They can occur for several reasons; a dramatic presentation with a sight‐threatening or life‐threatening illness, late presentation where the patient has not sought medical advice in a timely fashion, under‐treatment or delay in treatment through failure to appreciate the seriousness of the situation and sometimes through patient non‐compliance or refusal to accept appropriate treatment. Teifi James will explain his approach to minimise risk in these patients and avoid poor outcomes wherever this is possible. It is important to appreciate that some patients still have a bad outcome even if the treatment has been entirely appropriate.
Things to think about before choosing and submitting to a scientific journal
Authors: Stefansson Einar
Published: December 2019

With PUBMED and other search engines scanning scientific literature, the chances of your publication being seen by interested potential readers is vastly improved. You should only consider journals that are listed on PUBMED and other major search engines. The prestige of the journal is usually judged from the Impact factor. The impact factor evaluates the number of citations per article over 2 years and gives an indication of the scientific impact of the journal. There are other measures of impact. but this is the most popular one. Generally you want to select a journal with high impact factor, where you can reasonably expect your paper to be considered.
Vitreoretinal complications of uveitis. The role of vitrectomy
Authors: Vakalis Athanasios
Published: December 2019

The scope of vitreoretinal intervention in patients with uveitis has recently expanded. Therapeutic vitrectomy is performed to address complications such as visual loss from vitreous opacities, retinal detachment, development of epiretinal membranes, hypotony and also in certain cases to remove confined infective foci and assist in sustained drug delivery and diagnosis. While a plethora of studies report favorable outcomes of PPV in the management of uveitis, the quality of data remains poor, with a paucity of standardized reporting and limited prospective data. We will discuss our own experience and review the literature on each of the above surgical indications.
Effects of combined neuroprotective and regenerative agents on damaged retinal ganglion cells in vivo
Authors: Oshitari Toshiyuki , Kitamura Yuta , Guzel Bikbova , Baba Takayuki , Yamamoto Shuichi
Published: December 2019

Purpose

To estimate the effectiveness of a single or combined topical neurotrophic factors on damaged retinal ganglion cells (RGCs) in optic nerve crush (OCN) rat model.

Methods

The left ONC was used for achieving RGC degeneration in adult SD rats. Rats were divided into 7 groups with 6 animals in each group, depending on used therapeutic agents which had been administrated by instillations of 100 mm citicoline, 100 mm tauroursodeoxycholic acid (TUDCA), 10 ng/ml neurotrophin‐4 (NT‐4), combined TUDCA/citicoline (Doublet‐1), combined TUDCA/NT‐4 (Doublet‐2), combined TUDCA/citicoline/NT‐4 (Triplet) and PBS. After 2 weeks, the number of remaining RGCs was determined by Brn3a mouse antibody immunostaining of whole‐mount retinas. To examine the regenerative effect, cryosections of optic nerve were made and immunostained for anti ‐200 kD neurofilament heavy and GAP‐43 antibodies.

Results

The density of RGCs in the PBS group 2 weeks after ONC was significantly less than in the normal control. The density of RGCs in citicoline, TUDCA, Doublet‐1, Doublet‐2, and Triplet groups were significantly higher than that of RGCs in the PBS group. In the Triplet group, the density of RGCs was significantly higher than that in single drug treated eyes. Compared with the PBS group, the decrease in neurofilament immunopositive axon numbers were suppressed significantly in the combination eye drop treatment groups. In the Triplet group, the number of GAP‐43 immunopositive axons was greater than that in the PBS group. Neovascularization in cornea, iris, and retina were observed in 62% of eyes in the Doublet‐1 group.

Conclusions

Neuroprotective and regenerative effects can be achieved with topical instillations of combinations of neurotrophic agents. Adverse effects such as neovascularizations had been observed in the Doublet‐1 group. Further studies to identify the mechanisms of neovascularization development is need to be performed.
Outcomes and risk factor for failure after Aqueous Shunt Implants – annual review of one service results and benchmark
Authors: Puertas Renata , Susanna Fernanda , Shah Ameet , Murta Fabiola , Sood Vaneeta , Khalili Ashkan , Barton Keith
Published: December 2019

Purpose

Report annual benchmark exercise of aqueous shunt implants (tubes) outcomes and risk factors for failure over 4 years.

Methods

Retrospective cases series: Annual reporting of outcomes of tube implants. A total of 332 eyes were included in this study. The main outcomes were intra‐ocular pressure (IOP), loss of visual acuity (VA), number of medications and failure/visually threatening complications at 1‐year follow‐up.

Results

Surgical success rate was 93% at a mean follow‐up of 13.3 months. Compared to preoperative IOP (25.8 ± 7.9 mmHg), the mean postoperative IOP was significantly lower (14.4 ± 5.5 mmHg, p < 0.00001) on significantly fewer ocular hypertensive medications (from 3 ± 1 to 1.4 ± 1.3, p < 0.00001). There were 2 (0.6%) cases of loss of light perception.

Conclusion

Annual reporting of tube implant within a service provides an exceptional tool for monitoring outcomes in line with major literature. It allows to monitor safety as well as new trends in surgical technique.
Immune modulation following keratoplasty – current and future aspects
Authors: Pleyer Uwe
Published: December 2019

Penetrating keratoplasty (pkp) has definitely its paradoxes. It has been the first successful transplantation in man and is with approx. 100.000 grafts/year easily the most frequent allograft in human medicine. At the same time, it is still the least understood form of transplantation in respect to its biology. It is both, the most successful as well as probably the most underestimated procedure regarding its risks in clinical transplantation. Indeed, the common assumption, that pkp is a safe procedure with favourable prognosis. This may have hindered more intensive efforts of research in this field. There are still limitations to corneal transplantation, and allograft rejection still poses the greatest challenge. In the last two decades, graft survival has greatly improved by the introduction of efficient immunosuppressive drugs. This lecture aims to highlight the most novel and successful strategies to achieve a better outcome of pkp, e.g. the use of mesenchymal stem cells and tolerance induction via regulatory T cells.
The potent integrin antagonist THR‐687 is a promising next‐generation drug candidate for the treatment of multifactorial retinal diseases
Authors: Hu Tjing‐Tjing , Van Bergen Tine , Etienne Isabelle , Feyen Jean H. M. , Vermassen Elke
Published: December 2019

Purpose

Integrins are implicated in eye diseases such as diabetic retinopathy (DR) and wet age‐related macular degeneration (AMD). Targeting integrins can attenuate the main pathologic hallmarks like vascular leakage, inflammation, gliosis, angiogenesis and fibrosis. Previously, we showed that the integrin antagonist, THR‐687, has potent anti‐angiogenic properties in the cynomolgus choroidal neovascularization (CNV) model. The goal of this study was to further investigate the therapeutic effect of THR‐687 in the diabetic streptozotocin (STZ)‐induced rat model and the cynomolgus CNV model.

Methods

In STZ rats, 3 intravitreal (IVT) injections of THR‐687 (75 µg/eye) or vehicle were given with a weekly interval. Four weeks after diabetes onset vascular leakage, retinal inflammation and gliosis were analyzed by means of respectively FITC‐BSA perfusion, CD11b and vimentin staining. THR‐687 was investigated in the cynomolgus CNV model, by administering 3 IVT injections of THR‐687 (4.5 mg/eye, 2.25 mg/eye or 0.45 mg/eye) or vehicle with a weekly interval. Three weeks after laser induction the anti‐fibrotic and anti‐inflammatory potential of THR‐687 was studied by Sirius red and CD11b staining, respectively.

Results

IVT administration of THR‐687 in diabetic rats significantly decreased retinal permeability, inflammation and gliosis as compared to vehicle‐treated controls. In the cynomolgus CNV model, THR‐687 exhibited a dose‐dependent inhibition of collagen deposition in the laser spots, whereas only a trend towards decreased inflammation levels could be discerned with the highest dose level 3 weeks post‐laser.

Conclusion

THR‐687 potently antagonizes integrins implicated in vascular leakage, inflammation, gliosis, angiogenesis and fibrosis as demonstrated in the diabetic STZ rat and cynomolgus CNV models. Given its multifaceted mode of action and broad therapeutic potential, THR‐687 is a promising drug candidate for the treatment of vision‐threatening retinal pathologies such as DR and wet AMD.
The distribution of Keratometry in a population based study
Authors: Yekta Abbas Ali , Khabazkhoob Mehdi , Hashemi Hassan , Ostadimoghaddam Hadi , Heydarian Samira , Shandiz Javad Heravian
Published: December 2019

Purpose

To determine the distribution of keratometry values in a wide age range of 6–90 years.

Methods

In a Cross‐Sectional Study, samples were selected from two villages in Iran using multi‐stage random cluster sampling. After completing ophthalmic examinations for all cases, corneal imaging was done using Pentacam, and keratometry values were determined.

Results

Of the 3851 selected people, 3314 people participated in the study, and after applying the exclusion criteria, analyses were done on data from 2672 people. Mean age of the participants was 36.30 ± 18.51 years (from 6 to 90 years). Mean keratometry in flat and steep meridians was 42.98 (42.9–43.06) diopters (D) and 43.98 (43.91–44.07) D, respectively. Mean Mean‐K was 43.48 (43.41–43.56) D. Mean keratometry increased linearly up to the age of 70 years, and the cornea became slightly flat afterwards. Mean keratometry was significantly higher in females (P < 0.001). Myopic cases had the highest Mean‐K (P < 0.001). The correlation of mean keratometry with age, gender, central corneal thickness, anterior chamber depth, pupil diameter, and spherical equivalent was investigated in a multiple regression model. Only older age and female gender showed a significant association with mean keratometry. Overall, 31.62% (29.14‐34.09) of the sample had at least 1.0D of corneal astigmatism in this study.

Conclusions

This is one of the few studies worldwide that demonstrates changes in keratometry in a wide age range from childhood to old age. Results indicated that age and gender are variables associated with keratometry.
Self‐perforation of eye in patients with mental disorders
Authors: Klosi Jonida , Andrushkova Olga , Hrizhymalsk Kateryna , Kaminska Lina , Natalya Didik Natalya
Published: December 2019

Purpose

The purpose of the study was to inform ophthalmologists about the self‐perforation of the eye in patients with mental disorders based on a clinical case.

Methods

An overview, biomicroscopy of the ocular surface, ophthalmoscopy examination, ocular X‐ray examination, MRI, general‐clinical studies, consultation with psychiatrist and anesthesiologist.

Results

A schizophrenic young guy came with his mother in Ophthalmology department, the patient was catatonic and no cooperative, so no history could be obtained. Mother of the patient has noticed bloody discharge on pillow and in lower eyelid of the right eye.

External examination O.D: no changes in the eyelid, in the conjunctiva of the lower arch in the internal third there was noticed a limited hemorrhage, trauma of conjunctiva, the mobility of the eyeballs was not disturbed, the bottom part of the face was unchanged .

Antibacterial and anti‐inflammatory drops were prescribed (Signicef, Clodifen). On second day O.D: hematoma of the eyelid, chemosis of the conjunctiva, limitation of the eyeball movements, lack of the of the pupil reaction to the light, pallor optic disc, blindness. Under the skin in the projection of superior medial of orbit was palpated a foreign body with diameter 5 mm. O.S: hematoma of lower and upper eyelids and blindness. X‐RAY examination of the orbit: was noticed a foreign body measuring 4 by 2 mm which was localized in projection of the left orbit. MRI: was noticed the shadow of foreign body on the right orbit 4.5 by 0.5 mm which was localized near the inner wall of the orbit and reached its top, as a result damage 2/3rd of the right optic nerve. To the left of the orbit was determined the shadow of foreign body that intersects with the optic nerve. During the surgery half of the plastic pen was removed from the right orbit. On the left orbit was present the end of the pen ball (the other half of the pen) but was decided not to remove it. The psychiatrist found out that the patient had auditory hallucinations which ordered him to scratch his eyes, which he did by the pen. Total damage of the optic nerve of the right eye and damage of the rods on the left eye.

Conclusions

Patients with mental disorders are able to self‐attack and resulting in loss of the vision. In the absence of the contact the collection of anamnesis and diagnosis the problem it is complicated. In patients suspected of injuries it is recommended to be used all the methods of examinations so not to lose time.
Conjunctival bulbar redness (CBR) analysis to quantify inflammation in dry eye patients
Authors: Versura Piera , Interdonato Alberto , Giannaccare Giuseppe , Pellegrini Marco , Bernabei Federico , Moscardelli Fabiana , Coslovi Chiara , Guaraldi Fabio
Published: December 2019

Purpose

A red eye is common in the ophthalmic practice, and redness is one out of four cardinal signs of inflammation. The correlation between the conjunctival bulbar redness (CBR) and ocular surface parameters, including tear cytokine levels, was investigated, in patients suffering from Dry Eye (DE).

Methods

Thirty five patients diagnosed as suffering from DE and fifteen age and sex matched healthy volunteers and were analyzed with respect to: 1. subjective symptoms of discomfort with the Ocular Surface Disease Index (OSDI ranging 0‐100), and Visual Analogue Score (VAS, ranging 0‐100 mm) ; 2.Tear Film Break Up Time (TFBUT, seconds); 3. Corneal vital and conjunctival vital staining scored by the NEI system (score 0‐15, and 0‐18, respectively); 4. Tear levels of exudated serum albumin (ALBU, mg/ml), and of the following Interleukins (IL): IL1b. IL‐6. IL‐17A. and Tumor Necrosis Factor (TNF)a (pg/ml), detected by the Luminex Technology Multiplex Assays; 5. the quantification of CBR analyzed on slit lamp digital images by using image processing of relative Red‐channel activity with the free Image J software (NIH). Parameters were statistically analyzed in the two groups of subjects by using t‐test and Mann‐Whitney U test for parametric and nonparametric variables respectively. Relationship between variables was investigated using Spearman r correlation tests (significance p < 0.05).

Results

CBR was higher in DE as compared to controls (49.6 ± 3.5 vs 41.1 ± 2.4. p < 0.001). Tear IL‐6 level was higher in DE patients vs controls (25.5 ± 15.5 vs 5.9 ± 3.1, p < 0.0001), whereas IL1b, IL‐17A, and TNFa were detected in only the DE patients (median 5.73, 5.74, and 13.88 respectively) A significant correlation was found between CBR and IL‐6 (r = 0.524), TNFa (0.571) TFBUT (‐0.561), VAS score (0.832), and ALBU (0.628), p always <0.001.

Conclusions

Data suggests that digitized CBR analysis may be a useful tool to quantify inflammation in the clinical setting.
Randomized clinical study of the citicoline effect in glaucoma and glaucoma phacoemulsified patients
Authors: Μirachtsis Theodoros , Theofilou Georgia , Sorkou Konstantina , Lalias Theodoros , Marinopoulos Konstantinos , Sioulis Christos
Published: December 2019

Purpose

To examine the neuroprotective action of citicoline in the treatment of glaucoma and glaucoma phacoemulsified patients.

Methods

Fifty‐nine patients (118 eyes) with glaucoma were included in the study. Intraocular pressure (IOP) level <25 mmHg with or without treatment was the inclusion criterion. Thirty‐three patients received citicoline eye drops three times per day for 3 months and 26 received hyaluronic Na eyedrops, respectively. During the 3 months study all the patients underwent pachymetry and repeatedly IOP measurements, Visual Field Tests (VFT), Schirmer’s tests and OCT examination. Statistical analyses performed between the two groups, including further parameters, such as the severity of IOP, the visual field defects (MD value) and the presence of IOL.

Results

In patients with IOP < 15 mmHg, the citicoline group (n = 14) showed improved PSD value compared to hyaluronic Na group (n = 12; p = 0.003). In the 15–20 mmHg IOP patients, no changes noticed. In patients with 20 mmHg< IOP < 25 mmHg, the citicoline group (n = 10) showed higher RNFL (94.3 ± 11.2 μm) compared to hyaluronic Na group (n = 11, RNFL = 83.2 ± 11.7 μm; p = 0.029). In 16 eyes of the citicoline group, the RNFL appeared improved in the IOL eyes (p = 0.026).There were no statistical differences between the two groups regarding the severity of glaucoma, using the MD index in VFT.

Conclusion

Citicoline seems to act advantageously towards the RNFL index in the IOP > 20 mmHg and phacoemulsified patients, as well as the PSD index in patients with IOP < 15 mmHg.
The investigation of endothelial nitric oxide synthase (eNOS) activation in retinopathy
Authors: Ninchoji Takeshi , Love Dominic , Smith Ross , Claesson‐Welsh Lena
Published: December 2019

Purpose

To elucidate the role of endothelial nitric oxide synthase (eNOS) activation in the induction of vascular endothelial growth factor (VEGF)‐induced permeability, the underlying mechanism and the contribution to exaggerated vascular leakage in eye disease.

Methods

Retinal neovascularization and pathological edema in the superficial and deep retinal vascular plexa were investigated using the oxygen‐induced retinopathy (OIR) mouse model. eNOS activity was blocked either chemically by using the NO inhibitor or genetically by using mutant mice (Mut) in which serine 1176 in eNOS is replaced by alanine (Nos3S1176A/S1176A,therefore is unable to induce eNOS activity). Retina avascular area and proliferative vessel tuft formation were assessed at postnatal (P) day 17. Leakage was determined by injecting 25 nm fluorescent microspheres in the circulation followed by microscopy. Isolectin B4, eNOS, vascular endothelial cadherin (VEC), and phosphoY685‐VEC immunostaining was assessed by confocal imaging followed by image analysis using ImageJ. Students t‐test was used for statistical evaluation. p < 0.05 was regarded as statistically significant.

Results

Administration of the NO inhibitor during P12‐P17 reduced overall pathological tuft area (p < 0.05), and decreased the area of individual tufts (p < 0.01) compared to control. Mut displayed reduced neovascular tuft formation (p < 0.01) and decreased tuft size compared to wildtype mice (WT) (p < 0.05). Mice unable to activate eNOS displayed a junctional phenotype. Firstly, phosphoY685‐VEC in tufts was decreased in Mut compared to WT (p < 0.05). Secondly, immunostaining for eNOS colocalized with VEC in vessels of WT but not in Mut (p < 0.05). Thirdly, vascular leakage was reduced in OIR‐challanged Mut (p < 0.01).

Conclusion

Our data establish that eNOS is critical for VEC‐regulated endothelial junction stability and vascular leakage. Thus, eNOS is an important target for the development of therapeutic agents to treat eye disease.
Segmentation errors in OCT‐angiography associated with epiretinal membranes
Authors: Xirou Tina , Bontzos Georgios , Garnavou‐Xirou Christina , Kontou Eugenia , Gkizis Ilias , Kabanarou Stamatina
Published: December 2019

Purpose

To explore segmentation errors, image quality and motion associated artifacts in eyes with idiopathic epiretinal membrane (ERM).

Methods

Retrospective comparative study. We included 32 eyes from 32 patients affected by ERM, as well as 32 eyes from 32 healthy, age‐matched subjects. Optical coherence tomography‐angiography (OCT‐A) was performed in the right eye of healthy controls (65.82 ± 17.43 years) and on the eye with the most advanced clinically diagnosed ERM (69.53 ± 13.12 years). The device used in this study provides a set of reference planes automatically segmented by the integrated software including the internal limiting membrane (ILM), the inner plexiform layer (IPL), and the retinal pigment epithelium (RPE) reference. Segmentation was regarded as inaccurate if either segmentation deviated from the correct plane by more than 50 μm. Presence of motion artifacts (blink lines, displacement, stretch artifacts, quilting, vessel doubling) as well as image quality were reported.

Results

Mean image quality was 7.2 ± 0.9 for the ERM patients. Phakic eyes had a mean quality of 7.4 ± 0.8, and pseudo‐phakic eyes had a mean quality of 7.2 ± 0.6 (p = 0.107). Motion artifacts were 1.22 ± 0.7 in the study cohort. Segmentation was accurate in all healthy subjects (n = 32). Segmentation errors occurred in 65.6% of ERM patients. The IPL was the segmentation boundary most prone to inaccurate segmentation, followed by the ILM. Segmentation of RPE layer was accurate in 96.7% of all cases.

Conclusions

OCT‐A image quality is an essential aspect in clinical practice, however, in several cases it cannot be reproduced in pathological conditions and is prone to motion artifacts and segmentation errors. Incorrect segmentation results in anatomically incorrect en‐face OCT‐A images and consequently in false quantification measures. Even though manual segmentation can be performed, it is rather laborious and suffers from interobserver errors.
Effects of type 2 diabetes mellitus on gene expression profile of meibomian glands in mice
Authors: Yildiz Erdost , Zibandeh Noushin , Özer Berna , Sahin Afsun
Published: December 2019

Purpose

Diabetes mellitus (DM) is a major health problem and its complications cause blindness. Meibomian gland dysfunction and dry eye disease are also important ocular complications related with DM. According to our hypothesis, DM can exhibit significant altered gene expression in meibomian glands. To test our hypothesis, meibomian glands of leptin deficient spontaneous diabetic and non‐diabetic mice were extracted and gene expression profiles were analyzed with microarray.

Methods

Nine Lepob/ob spontaneous diabetic mice and nine non‐diabetic Balb/c mice (control group) were used. Blood glucose levels, tearfilm break‐up time and fluorescein scores were measured for 12 weeks. Meibomian glands were dissected and RNAs were isolated for microarray gene expression analysis. Probes with standard deviation more than 0.1 were filtered and used 40 452 of 45 281 probes for processing. Fold change analysis were performed and identified for affected genes, and impact of genes on proteins, pathways and gene ontologies were analyzed by using various databases.

Results

We observed 172 up‐regulated and 118 down‐regulated genes in type‐2 diabetic mice when compared to non‐diabetic mice. Interestingly, expression of collagen type‐I, integrin beta‐I binding protein‐I, pyruvate dehydrogenase kinase, TNF receptor genes up‐regulated with DM; on other hand, IL‐33, cholecystokinin, plasminogen activator, IL‐1 and serine peptidase inhibitor genes down‐regulated significantly. Also, we have seen significant decrease in WNT signaling and pentose phosphate pathways related genes.

Conclusion

Our data shows these changes in gene expression caused by endocrine and immune mechanisms of type‐2 DM which result disrupted homeostasis of epithelial cells of MG. Increased expressions of apoptosis and inflammation related genes and their effects on related pathways have proven that meibomian glands were negatively affected from type‐2 DM.
Necrotizing scleritis after “pterygium” excision with mitomycin C
Authors: Friesacher Anna , Alder Marco , Rüesch Rheinhard , Valmaggia Christophe , Todorova Margarita
Published: December 2019

Purpose

Application of Miitomycin C during pterygium excision is discussed to reduce its recurrence rate. Nevertheless, potential adverse effects of Mitomycin C application should be evaluated in each individual patient.

Method

We report on minimal invasive procedures applied in a case of scleral necrosis following pterygium excision combined with intraoperative application of Mitomycin C. A 87‐year old man presented for a second opinion having suffered a severe ocular pain on the left eye for the last three weeks after pterygium surgery. At presentation, a gradual thinning of the sclera spreading to the adjoining cornea was observed. In addition, signs of chronic blepharitis with a dysfunction of the marginal eyelid glands, as well as, a negative Bell’s sign were observed on both eyes.

Results

Local lubrication was applied, supported by broad‐spectrum local antibiotic therapy. In order to prevent perforation and strengthen the corneal stroma, doxycycline 100 mg daily, was added. The initiated systemic prednisone treatment was reduced to 20 mg daily. In addition, to support sufficient eyelids closure in the presence of negative Bell’s phenomenon, 20 units Botox was applied. Within the following days a gradual remission was achieved; with reduction of necrotic area and perilimbal ischemia, supporting thus, the corneal thickening and consequently the symptomatic pain release. Furthermore, histological results of the excised pterygium revealed conjunctival tissue with focal metaplasia of the squamous epithelium, stromal fibrosis, elastosis, and a small amount of conjunctival calcification, findings compatible with pinguecula on atypical location.

Conclusion

The presented case confirms that application of mitomycin C should be used with consideration in patients featuring pre‐existing trophic anterior segment disease and/or systemic disease predisposing to wound‐healing impairment.
Upregulation of the mu‐opioid receptor in the cornea and trigeminal ganglion following corneal inflammatory pain
Authors: Guerrero Moreno Adrián , Joubert Fanny , Fakih Darine , Baudouin Christophe , Mélik Parsadaniantz Stéphane , Réaux‐Le Goazigo Annabelle
Published: December 2019

Ocular pain following corneal injury is frequently observed in clinic, but its management remains as therapeutic challenge. The innervation of the cornea is provided by sensitive neurons located in the ophthalmic branch of trigeminal ganglion (TG). We recently reported that increasing endogenous enkephalin levels reduced ocular pain in a opioid receptor‐mediated manner (Reaux‐Le Goazigo et al., 2019). As the expression of the mu opioid receptor (MOR) in the cornea and TG is not known, this work aims to study MOR distribution both in control and under inflammatory pain conditions.

Methodology

Adult male mice were submitted to a corneal scraping followed by 10 μL of lipopolysaccharide (LPS) at day 1 and day 3. Mechanical corneal sensitivity was measured by Von Frey filaments and corneal integrity was evaluated with in vivo confocal microscopy (IVCM). At D5, animals were perfused with 4% PFA to study the MOR expression by immunofluorescence (IF) and in situ hybridization (RNAscope method) in the ipsilateral cornea and TG. Images were captured with a confocal microscope and staining was quantified using imageJ.

Results

A corneal scraping and LPS instillation induced a mechanical corneal hypersensitivity compared to control mice. IVCM images showed a superficial epithelium alteration and inflammatory cells. IF experiments highlight the presence of MOR in corneal nerve fibers in both groups of animals but an increase of MOR immunoreactivity was noted in scraping + LPS mice. At the level of the ophthalmic branch of TG, MOR (protein and mRNA) was detected in a large population of primary sensory neurons. Quantification of MOR mRNA signal revealed a significant (+60%) increase of the receptor following corneal pain.

Conclusion

This study provides novel information about the distribution of MOR in the cornea and TG in control and under corneal pain condition. Altogether, these results suggest that MOR could constitute a new therapeutic target for inflammatory ocular pain.
Protein cages modified for oligonucleotide delivery to retinal cells
Authors: Pretto Chiara , van Hest Jan
Published: December 2019

Purpose

Investigation on the applicability of Virus‐like particles (VLPs) based on the Cowpea Chlorotic Mottle Virus (CCMV) for the selective treatment of age‐related macular degeneration (AMD) exploiting RNAi technology.

Methods

Anti‐luciferase siRNA was selected as a prototype cargo (Luciferase GL3 Duplex, Dharmacon). CCMV‐siRNA loaded nanoparticles were formulated and stabilization of the protein scaffold was achieved by crosslinking the particle surface with a disulfide containing crosslinking agent DTSSP (3,3′‐dithiobis[sulfosuccinimidylpropionate], Thermo Fisher). Particles were characterized by Transmission Electron Microscopy, Dynamic Light Scattering and Size Exclusion Chromatography. CCMV‐induced siRNA protection against enzymatic digestion with benzonase was assessed exploiting agarose gel electrophoresis. The efficacy of siRNA‐loaded nanoparticles was investigated in vitro exploiting the luciferase assay kit (Promega).

Results

siRNA‐loaded CCMV spherical nanoparticles of 28 nm in diameter were formulated. A 20:1 DTSSP: CP molar ratio was found to be optimal for particle crosslinking and stabilization in physiological conditions. Crosslinked siRNA‐loaded particles showed to be stable at 37°C for at least 12 hr. The drug delivery system showed the capability to protect encapsulated siRNA from degradation. A loading efficiency of 56% corresponding to 22 siRNA molecules per capsid was assessed. Particles incubated with Lipofectamine2000 were able to effectively knock down luciferase expression in HeLa‐Luc cells.

Conclusions

CCMV nanoparticles represent an innovative platform for oligonucleotide delivery to the posterior segment of the eye due to their dynamic structure, high loading capacity as well as their cargo protective effect.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie grant agreement No 722717.
Evaluation with angiography by optical coherence tomography of patients with multiple sclerosis
Authors: Cordón Ciordia Beatriz , Pérez Velilla Javier , José Vicente Altabas Maria , Viladés Palomar Elisa , Orduna Hospital Elvira , Pérez ‐ Del Palomar Amaya , Cegoñino Banzo Jose , Montolio Marco Alberto , Ramón Ara Callizo Jose , Jesus Rodrigo Sanjuán Maria , Satué Palacián Maria , García‐Martín Elena
Published: December 2019

Purpose

To evaluate the microvascular changes in the superficial plexus of the retina and peripapillary plexus in patients with relapsing‐remitting multiple sclerosis (RR MS) by optical coherence tomography angiography (OCT‐A).

Method

A prospective study was performed in a total of 75 patients. The control group consisted of 84 eyes of 42 subjects without any ocular disease. The study group was formed by 66 eyes of 33 patients with RR MS. Visual function was evaluated by visual acuity with Bailey‐Lovie optotype and contrast sensitivity with Pelli Robson test. The Deep Range Image (DRI) Triton, Swept Source OCT (Topcon Eye Care Company) was used to analyze vascular density of superficial plexus of the retina and the peripapillary area using (OCT‐A).

Results

The nasal, temporal, superior and inferior parafoveal areas of RR MS patient group showed a significant decrease in vascular flow compared with the control group (p = 0.024, 0.039, 0.001 and <0.014 respectively). No significant differences were found in the peripapillary plexus between controls and patients groups.

Conclusions

There is a vascular reduction in the macular zone at the superficial plexus level in patients suffering RR MS.
Impact of OCT and visual function in multiple sclerosis patients treated with Fingolimod
Authors: Pérez‐Velilla Javier , José Vicente María , Vilades Palomar Elisa , Orduna Hospital Elvira , Cordón Ciordia Beatriz , Gil‐Arribas Laura , Ruiz De Gopegui Erika , Jesús Rodrigo María , Satué Palacian María , García‐Martín Elena
Published: December 2019

Purpose

To evaluate the effect of Fingolimod during one year on the neuro‐retinal structures and visual function in patients with multiple sclerosis (MS).

Methods

Seventy eight eyes of 78 patients with MS treated with Fingolimod were evaluated every 3 months (for a year) and compared with 32 MS patients treated with Interferon. All subjects underwent visual acuity (VA) test for high and low contrast (100%, 2.5% and 1.25%), contrast sensitivity vision (using the CSV‐1000 and Pelli‐Robson tests), color vision (using the Fansworth and L'Anthony D15 desaturated tests), the thickness of the retinal fiber layer, the ganglion cell layer and the macula by Fourier‐domain optical coherence tomography (OCT).

Results

In MS patients treated with Fingolimod, a decrease in visual acuity was registered in 100% and 1.25% contrasts (p = 0.009 and p = 0.008respectivelly), as well as a reduction in contrast sensitivity in the Pelli‐Robson test (p < 0.001). Structurally a decrease in the ganglion cell layer (p = 0.008) and an increase in macular thickness (p = 0.006) were found. In MS patients treated with Interferon there is a significant decrease only in ganglion cell layer thickness (p = 0.006), being this decrease higher than in the Fingolimod group (P < 0.006).

Conclusions

Treatment with Fingolimod causes a significant decrease in visual acuity and contrast sensitivity. It also causes an increase in average central macular thickness compared to the Interferon treatment. It's probable that the increase in central macular thickness is the cause of changes in visual function.
Rapid healing with ReGeneraTing Agent (RGTA) of a refractory post surgical corneal ulcer
Authors: Le Aurélie , Makhoul Dorine , Willermain François , Postelmans Laurence , Caspers Laure
Published: December 2019

Purpose

Corneal ulcer, especially in the context of neurotrophic keratopathy is a potentially challenging and sight threatening condition. We present a case of refractory post‐surgical ulcer with decreased corneal sensitivity, successfully treated with RGTA (Cacicol®).

Methods

A 95 years‐old man underwent eyelid surgery for basocellular carcinoma. Because of a secondary eyelid malocclusion, a band keratopathy developed, leading visual acuity to 3/10. Two EDTA scratching surgeries were performed in order to improve vision. But six weeks after the last surgery, a partial loss of sensitivity associated with an epithelial defect (1.5 mm*2.5 mm) and deep stromal ulcer (with stromal edema all around and temporal neovascularization) was still present despite an intensive treatment with artificial tears, vitamine A ointment, antibiotic drops, 24‐hr bandage with a topical antibiotic cream: oxytetracyclin‐ polymyxin and hydrocortisone (Terracortril®). For this refractory corneal ulcer with neurotrophic keratitis, we then decided to stop this treatment and to replace it by RGTA 1*/48 hr and artificial tears 5*/day.

Results

While it did not respond to previous topical treatments for six weeks, this post‐surgical ulcer with decreased corneal sensitivity and exposed cornea, responded quickly to RGTA drops. After one week, the size of the ulcer was a fifth from its original size. It took fifteen days to completely close the ulcer.

Conclusion

The healing of corneal ulcers especially when the corneal sensitivity is involved with a consequent neurotrophic keratitis is a challenge. Several steps are necessary: to stop topical toxic treatment, to find and to treat causes of the ulcer and then apply and alternative treatment. In some cases, RGTA drops can quickly help.
Anti‐glaucomatous preparations and effect on human conjunctival goblet cells
Authors: Hedengran Anne , Begun Xenia , Müllertz Olivia , Mouhammad Zaynab , Vohra Rupali , Petrovski Goran , Kolko Miriam
Published: December 2019

Purpose

To investigate goblet cell (GC) survival after treatment with benzalkonium chloride (BAC)‐preserved anti‐glaucomatous eye drops. Conjunctival GCs produce mucin which stabilizes the tear film and protects against dry eyes. Eyedrop‐induced GC death may cause ocular surface disorders.

Method

Latanoprost Teva (LT; prostaglandin analogue), Optimol® (OP; beta‐blocker), Dorzolamid Stada (DS; carbonic anhydrase inhibitor) and Brimondine tartrat Teva (BT; alfa2‐agonist) BAC‐preserved eye drops were used for treatment of ex vivo cultivated human GCs. The cell survival was evaluated by lactate dehydrogenase assay on human GCs after 30 min and 6 hr exposure to the different treatments and compared to the untreated control group. pH‐value and osmolality were also measured.

Results

After 30 min of treatment, the human GC survival was 69.05% for LT, 69.78% for OP, 71.12% for DS and 93.42% for BT. The survival was significantly reduced only for the treatment with LT compared to the controls (p = 0.044). After 6 hr of exposure, GC survival was 31.08% for LT, 33.81 % for OP, 51.64 % for DS and 74.49 % for BT. The survival was significantly reduced for LT, OP, and DS compared to controls (p = 0.002, p = 0.004, p = 0.022). DS had the lowest pH (5.58), while OP the highest (6.84). LT had the lowest osmolality (267.6 mOsm/kg), while BT had the highest (293.2). There was no apparent correlation between GC survival, pH and osmolality. However, there seemed to be a connection between GC survival and BAC concentration. LT caused the lowest survival with a BAC concentration of 0.02%, while OP had a concentration of 0.01%, DS of 0.0075% and BT of 0.005%.

Conclusion

Latanoprost Teva was the most cytotoxic, causing significant GC death after 30 min and 6 hr of treatment. OP and DS caused significant GC death only after 6 hr of exposure. BT did not affect the GC survival. The cytotoxicity appeared to correlate with the BAC concentration, but not pH and osmolality.
Visual changes in patients with early type 2 diabetes mellitus without diabetic retinopathy due to possible subclinical ischemia
Authors: Vicente María José , Vilades Elisa , Orduna Elvira , Cordón Beatriz , Pérez‐Velilla Javier , Melchor Isabel , Gil‐Arribas Laura , Rodrigo María Jesús , Satué María , García‐Martín Elena
Published: December 2019

Purpose

To assess visual changes in patients suffering from early type 2 diabetes mellitus (DM2) with good metabolic control and without diabetic retinopathy as a possible implication of subclinical ischemia.

Method

Sixty patients with early DM2 with good metabolic control and without diabetic retinopathy and sixty age and sex‐matched healthy controls were recruited for the study. Only one eye per subject was randomly selected and included. Psychophysics tests were performed as visual acuity (VA) by ETDRS charts, colour vision using the Farnsworth and L’Anthony D15 desaturated colour tests, contrast sensitivity vision (CSV) using Pelli Robson chart and CSV 1000E test and visual field with the automated Easyfield perimeter. Systemic parameters such as the presence or absence of vascular complications and the HbA1c levels were recorded, as well as the disease duration.

Results

Patients with DM2 showed worse VA at low contrast level (2.5%, p = 0.002; 1.25%, p = 0.007), worse CSV at high spatial frequencies (12 cpd, p = 0.007; 18 cpd, p = 0.011) and worse colour vision (Farnsworth, p = 0.006; Lanthony, p < 0.001) recordings compared to the control group. However, visual field parameters were similar in both groups. Patients with more than 10 years of disease duration obtained lower results with the ETDRS test, and those ones with systemic vascular complications got worse results in CSV and colour vision tests (CSV 18 cpd, p = 0.024; Lanthony test, p = 0.014). There were no significant differences between patients with HbA1c levels higher versus lower than 7%.

Conclusions

Patients with early DM2, with good metabolic control and no diabetic retinopathy showed visual dysfunction compatible with retinal neurodegeneration. Subclinical ischemia could contribute to neuronal damage, before than the evident vascular changes appear.