bluuebunny/crossref_metadata_2025 huggingface dataset:
Slow Mohs surgery for the treatment of periocular basal cell carcinomas, three and five year follow‐up
Authors: Thornton Richard , Makuloluwe Sarith , Rogers Simon , Maclean Hunter
Published: December 2019

Purpose

Basal cell carcinoma (BCC) is the most common skin malignancy, disproportionately occurring in sun exposed areas, such as the eyelids. Whilst surgical excision is considered the most effective method for treating periocular BCCs, there is a paucity of evidence as to which surgical technique is the most appropriate. Mohs micrographic surgery is likely superior to traditional surgical excision in achieving clear excision margins and sparing tissues, but requires immediate access to histology. Slow Mohs surgery offers an alternative when immediate histology is unavailable, as tumour excision and reconstruction are performed in two separate procedures. In this retrospective case series is reported the 3 and 5 year outcomes following Slow Mohs surgery.

Methods

193 consecutive patients who had undergone Slow Mohs surgery, between January 2009 and December 2015 at a large district general hospital were identified retrospectively using electronic theatre records. Electronic lab reports and patient records were then utilised and the data analysed using EXCEL and SPSS.

Results

160 patients had a diagnosis of BCC or basosquamous carcinoma. Following exclusions, 141 survived to be included in the 3 year recurrence cohort. Of these, 2.83% had recurred at 3 years. A smaller group of 72 patients survived and had follow‐up lasting 5 years, within this group there was a recurrence rate of 4.16%.

Conclusion

Slow Mohs potentially achieves recurrence rates comparable to Mohs micrographic surgery, offering an alternative should immediate histological examination not be available. There currently exists little evidence comparing the techniques prospectively, nor is there cost comparison between them.
Electrophysiological methods‐ exact diagnostics in ophthalmology
Authors: Stetinova Tamara
Published: December 2019

Goal

After short theoretical introduction, explaining the basic principles of electrophysiological investigation, the authors show a few case reports. They analyze the results of investigation in the group of patients, who suffer from various eye diseases.

They compare the various subjective and objective symptoms, that should either correlate to electrophysiological exam, or not.

The authors ask in their subject, if the diagnostics of eye disease could be better and sooner using the electrophysiological tests, while they are able to test the visual pathway.

Material and methods

Five members of the same family were examined in electrophysiological laboratory. They had passed the examination, both standard methods, such as full field ERG, PVEP and FVEP and special multifocal ERG. The basic investigation, such as visual acuity, panfundoscopy, fluorescein angiography was done previously.

One member of the family had noted some subjective disorders, such as low vision, visual field defects, colour vision disorders. Others were relatively asymptomatic.

The results were summarised.

Results

In all members, completely, were detected various forms of ocular pathology, from retinal and optic nerve damage to the brain disorder, though they were relatively asymptomatic. The first symptoms of hereditary disease were present.

In patients we have detected some forms of ocular pathology, from peripheral retinal degeneration, macular degeneration, choroidal pathology to the optic neuropathy.

In some probands hereditary dystrophies were validated.

The explicit concordance between subjective and objective symptoms and ERG results is not a rule.

Conclusion

We are sure, that electrophysiological investigation methods could represent the base of exact diagnostics. When we should find the subject, that suffers from hereditary eye disease, the active seeking in complete family is very important and necesary. In many cases and forms of ocular pathology, some causal treatment, such as intravitreal therapy, does exist
Non‐arteritic anterior ischemic optic neuropathy due to hypovolemia
Authors: Bontzos Georgios , Gkoumas Evangelos , Xirou Tina , Chatzispasou Efterpi , Kabanarou Stamatina
Published: December 2019

Purpose

To present a case of non‐arteritic anterior ischemic optic neuropathy due to hypovolemia.

Methods

A 54 year‐old male was referred to the ophthalmology department with a history of blurred vision in his right eye following acute bleeding due to duodenal ulcer 5 days ago. Complete ophthalmological examination was performed, including best corrected visual acuity (BCVA), visual field, optical coherence tomography (OCT) and OCT‐angiography (OCT‐A).

Results

His BCVA was 3/10 in his right and 2/10 in his left eye (history of amblyopia since childhood). Fundus examination of his right eye revealed optic disc edema and peripapillary flame‐shaped hemorrhages with cotton wool spots nasally to the fovea. There were only a few flame‐shaped hemorrhages at the peripapillary area in his left eye. OCT imaging of his right eye revealed an area of increased reflectivity mainly at the inner retinal layers associated with small increase in retinal thickness nasally to the fovea. A month later OCT documented reduced retinal thickness at the aforementioned area, where in OCT‐A there was capillary drop out, mainly at the deep capillary plexus, with decreased vascular density. Visual fields revealed generalized depression in OD with minimal findings in OS. Based on the above, the diagnosis of non‐arteritic anterior ischemic optic neuropathy following acute blood loss was set. The patient received blood transfusion immediately after his hospital admission. Although his general symptoms improved shortly after treatment there was only a partial visual recovery as decreased vascular perfusion was persisting four months later. Long‐term anticoagulation therapy was also given to the patient.

Conclusions

Patients reporting blurred vision after acute massive bleeding that could lead to hypovolemia should be investigated for ischemic optic neuropathy. OCT‐A helps monitoring vessel abnormalities in areas of compromised blood perfusion and may explain poor visual outcomes in such cases.
Basal neuro‐immune interactions between resident dentritic cells and corneal sensory nerves
Authors: Rincon‐Frutos Laura , Luna Carolina , Acosta M.Carmen , Belmonte Carlos , Hamrah Pedram , Seyed‐Razavi Yashar , Gallar Juana
Published: December 2019

Purpose

To determine the influence of dendritic cells (DCs) in modulating corneal sensory nerve activity at basal conditions using a DC‐depletion mice model.

Methods

C57BL/6 CD11c‐DTR mice (5‐6 month old) of both sexes were used. The effect of short‐term (2 days) and long‐term (8 days) DC depletion on corneal sensory nerve activity was studied in eyes following bilateral temporal and nasal subconjunctival injections of diphtheria toxin (DT) in anesthetized animals. Nerve terminal impulse (NTI) activity of corneal cold thermoreceptor endings was recorded in excised eyes continuously superfused with saline solution at 34ºC. Background and stimulus‐evoked (cooling and heating ramps) activity was studied. Naïve (no DT injections) CD11c‐DTR mice served as controls.

Results

Short‐term DC depletion produced a significant decrease in heating threshold (37.65±0.66 ºC, n=10; p=0.003, ANOVA) compared with naïve (41.57±1.77 ºC, n=4) and long‐term DC depletion conditions (42.27±0.97 ºC, n=8). However, long‐term DC depletion seemed to desensitize cold responses of sensory nerve endings, with higher cooling threshold and temperature to reach the peak frequency during the cooling ramp (30.65±0.48 ºC, n=17 vs. naïve, 32.31±0.29 ºC, n=20 and short‐term DC depletion, 32.2±0.44 ºC, n=17; p=0.005, ANOVA). Besides, in long‐term DC depleted eyes, NTI shape was altered: duration of NTIs was significantly increased (1.9± 0.06 ms, n=16; p=0.009, ANOVA) compared with naïve (1.5± 0.1 ms, n=18) and short‐term DC depleted eyes (1.7± 0.1 ms, n=11), having both longer depolarization and repolarization times.

Conclusions

The differences observed in both NTI firing and spike shape of cold nerve endings, suggest that depletion of resident DC alters corneal sensory nerve activity, therefore supporting the idea of a neuro‐immune interaction at basal conditions.

(Support: SAF2017‐83674‐C2‐2‐R and ‐1‐R, AEI, Spain, and ERDF, EU; ACIF/2017/169 Fellowship from Generalitat Valenciana‐FSE to LR‐F)
Vasoproliferative retinal tumors in children and adults
Authors: Hadjistilianou Doris , De Francesco Sonia , Menicacci Cristina , Barchitta Matteo , Esposti Giulia , Serov Yuri
Published: December 2019

Purpose

Vasoproliferative tumors of the retina (VPTR) are benign lesions of unknown origin that may occur isolated (primary) or in association with other ocular conditions (secondary). They may be unilateral or bilateral and have a predilection for the peripheral inferior temporal quadrant of the retina. Retinal vasoproliferative tumors may be present at any age, although the majority are present in the third and fourth decades of life.

Methods

The authors report a personal series of cases in young children and adults either idiopathic or secondary to a pre‐existing ocular disease (retinitis pigmentosa and Nf1).

Results

Clinical findings, imaging, therapeutic options and outcome are reported.

Conclusions

Retinal vasoproliferative tumors may be idiopathic (74%) or secondary to a pre‐existing ocular diseases (26%). The fundus quadrant location in these tumors is curiously weighted toward the inferotemporal region. Despite this, these tumors may effect the visual activity because of the associated retinovitreal findings, such as subretinal and/or intraretinal exudation, subretinal fluid, vitreous hemorrhage, preretinal macular fibrosis and macular edema.
Comparison of peak times of photopic flicker electroretinogram responses recorded using conventional and portable systems in Birdshot chorioretinopathy
Authors: Pekacka Aleksandra , Hobby Angharad , Chow Isabelle , Indusegaran Mathura , Hammond Christopher , Stanford Miles , Mahroo Omar
Published: December 2019

Purpose

Assessing disease activity in Birdshot uveitis can be challenging. The peak time of the 30 Hz flicker photopic electroretinogram (ERG) was shown to be sensitive for detecting retinal dysfunction. ERG testing is not readily available in many eye units. We investigated use of a portable device to obtain recordings in the clinic setting and compared these with conventional recordings.

Methods

Patients underwent testing with the portable device (RETeval, LKC Technologies) and conventional equipment (Espion ColorDome, Diagnosys). For portable recordings pupils were undilated and skin electrodes used; for conventional recordings a conductive fibre electrode was used with mydriasis. Flicker ERG peak times were recorded and were deemed abnormal if they exceeded the 95th centile from a healthy cohort (>190 healthy volunteers).

Results

18 patients with Birdshot uveitis underwent recordings. Recordings with the portable device took c. 3 min and were well‐tolerated. Mean (SD) age was 56.3 (12.8) years. For portable recordings, mean (SD) peak times were 30.1 (3.7) and 30.2 (3.9) ms for right and left eyes respectively. For conventional recordings mean (SD) peak times were 31.4 (3.9) and 31.8 (4.0) ms respectively. Peak times were significantly shorter with the portable device (p = 0.026 and 0.002 for right and left eyes). Correlation between devices was high (0.83 and 0.89 for right and left eyes) and highly significant (p < 0.0001). Strength of agreement between the two methods was good (kappa statistic 0.64; 95% CI, 0.36‐0.92).

Conclusions

Correlation between the portable and conventional ERG recordings was high with a good level of agreement. Recordings were rapid and well‐tolerated. There were significant differences in peak times between the two methods highlighting the importance of normative data specific to each device.
Curry to treat Alzheimer’s disease?
Authors: Shamsher Ehtesham , Guo Li , Davis Benjamin M. , Luong Vy , Ravindran Nivedita , Somavarapu Satyanarayana , Cordeiro M. Francesca
Published: December 2019

Purpose

Alzheimer’s disease (AD) is the major cause of dementia in the world with increasing evidence of the retina being affected. Since no cure exists, the development of new treatments is an urgent unmet need. Curcumin, a natural polyphenol found in curry, has been advocated as a potential neuroprotectant in AD. However, its poor solubility in water and low bioavailability, have limited its clinical translation. In this study we describe a novel curcumin nanoparticle (CN) formulation and evaluate its neuroprotective efficacy in vitro and in vivo.

Methods

CNs were formulated using a thin film rehydration technique. R28 cells were used to assess CN neuroprotective activity. For in vivo studies 10‐month‐old 3xTg‐AD mice were treated intranasally 5 days/week with 3 μl of either CNs (n = 7) or vehicle (n = 6). After three months of treatment, animals had DARC (Detection of Apoptosing Retinal Cells) imaging and their brains (amyloid‐beta) were immunostained. All results are given with the standard error and the statistical test used is a student T‐test.

Results

CN formulation incorporating over 4 mg/ml of curcumin was stable over 90 days. CNs protected R28 cells against a) glutamate excitotoxicity with an IC50 of 22.36 ± 0.50 mm versus 4.54 ± 0.32 mm for control group (p < 0.0001) and b) hypoxia mimetic cobalt chloride with an IC50 of 427.9±37.62 μm versus 259.4 ± 15.34 μm for control group (p < 0.05). No adverse effects were seen in vivo either systemically or in the eye. 3xTg‐AD mice receiving CNs were found to have a significant reduction in the DARC count (p < 0.05) compared to vehicle controls (17.36 ± 3.34 versus 49.08 ± 13.28). Their brains had a reduction in Aβ deposition score compared to vehicle controls (3.61 ± 0.17 versus 4.47 ± 0.23, p < 0.01).

Conclusions

These promising results suggest that systemic CN has a potential therapeutic effect in AD, and that the effects of AD therapy can be assessed through the eye.
RESVEGA in exudative age–related macular degeneration ‐ the next well‐documented clinical case
Authors: Kubicz Anna
Published: December 2019

Purpose

This clinical case aims to present the improvement of retinal structure and stabilisation of visual acuity using RESVEGA (trans‐resveratrol and omega‐3 fatty acids i.a.) in a patient with exudative AMD.

Methods

A 62‐year‐old patient reported to the Ophthalmology Clinic because of sight deterioration in the left eye. The patient was not treated for eye diseases before and not treated for systemic diseases. Anterior segments of the left and the right eye without changes. Fundus oculi: in the right eye – drusen at the macula; in the left eye: elevation in the fovea, drusen. Otherwise fundus oculi unremarkable. Additional diagnostic tests (OCT, angiography) were recommended. The presence of subretinal fluid was confirmed in the left eye. The patient did not agree to intravitreal injections of anti – VEGF. Supplementation with Resvega (trans‐resveratrol and omega‐3 fatty acids; a single dose of 2 capsules per day taken with a meal) was recommended.

Results

A regression of the subretinal fluid was obtained after administration of Resvega, although anti‐VEGF treatment was not administered. The changes were documented in OCT and AF. Oral supplementation allowed to improve and then maintain the local condition and visual acuity for nearly four years.

Conclusion

The presented case is another well‐documented case of subretinal fluid regression in exudative AMD after Resvega supplementation. The author presented a similar case during the EVER convention in 2016 (patient with AMD, 9‐month observation). In the present case, the improvement and more than three years of ophthalmic stabilisation have been documented. The presented case shows that it is worth considering supplementation with Resvega (2 tablets per day in a single dose) in case of patients with exudative AMD.The effect of resveratrol and Omega 3 acids on exudative AMD requires further research.
Clinical spectrum of atypical ocular toxoplasma chorioretinitis
Authors: Carreño Ester , Burke Tomas , Amir Zain , Hickman Casey Thomas , Lee Richard , Dick Andrew , Ross Adam
Published: December 2019

Purpose

To describe the clinical spectrum of patients with atypical ocular toxoplasmosis, requiring confirmatory diagnosis with PCR (due to uncommon clinical presentation or non‐response to conventional treatment).

Methods

All cases with confirmed positive PCR for Toxoplasma gondii seen in the Bristol Eye Hospital over the last 5 years were retrospectively reviewed for patient demographic, known systemic immunosuppression, clinical presentation, response to treatment and recurrences/complications.

Results

A total number of 16 patients were included. Five of which were immunocompromised. Bilateral disease was seen in three cases (18.7%). The mean age at diagnosis was 64.9, with 37.5% female and 62.5% male patients. 10 out of the 19 affected eyes (52.6%) had multifocal lesions with 9 eyes (47.4%) having an isolated lesion. Eleven patients (one bilateral) had fluorescein angiography during their follow‐up, which confirmed the presence of vasculitis in nine of those eyes (75%) with five of these having occlusive vasculitis (41.7%). Of the twelve patients treated with azithromycin as first line, only 4 (25%) showed a response to treatment.

Conclusions

PCR is warranted to identify cases of atypical ocular toxoplasmosis. These atypical forms were also seen in immunocompetent patients. Although azithromycin has been proved to be an alternative therapy in the treatment of ocular toxoplasmosis, we identified a lack of response to azithromycin in 75% of patients in our series of patients with atypical ocular toxoplasmosis.
Short and long term results of the first xen45 implanted in our service
Authors: Antonio Miralles de Imperial‐Ollero Juan , Caravaca‐Alegría Almudena , María Caracena‐Ordóñez José , Javier García‐Medina José , Paz Villegas‐Pérez María
Published: December 2019

Purpose

To evaluate the surgical experience and the short and long‐term safety and efficacy of the first XEN45 implanted in our Service.

Material and Methods

We included the first 9 eyes of seven patients that received a XEN45 implant in our Service by two different surgeons. All the patients were diagnosed with primary open‐angle glaucoma (POAG) that was uncontrolled with medical treatment and were pseudophakics. Three had before a superior trabeculectomy. We evaluated pre and post‐surgery: intraocular pressure (IOP), number of ocular hypotensive drugs needed, visual acuity and retinal nerve fiber layer (RNFL) thickness. We reviewed also the difficulties and complications events encountered during surgery and the implant position and bleb characteristics (IBAGS) 1,7 and 15 days, 1,3,6, and 12 months after surgery.

Results

Mean IOP before surgery was 22.33 ± 6.20 mm Hg and the mean number of ocular hypotensive medications 3.11 ± 0.93. One, 7, 15, days and 1,3,6 and 12 months after surgery, the mean IOP were, respectively 10.55 (n = 9), 13.44 (n = 9), 16.14 (n = 7), 16.20 (n = 5), 15.75 (n = 8), 19.57 (n = 9) and 14.33 (n = 5). One year after surgery, the mean number of ocular hypotensive medications was 1.33 (n = 5) There were only four intraoperative complications: two eyes had a small bleeding at the iridocorneal angle, in one eye the segment of the implant in the anterior chamber was too long and was cut in the moment of the surgery and in one eye the subconjunctival end of the bleb was bent and not functional and therefore was accessed externally three weeks later. No postoperative complications were observed and no further glaucoma surgeries were required during follow‐up.

Conclusion

The first XEN45 devices implanted in our Service have shown a good safety and efficacy for the treatment of pseudophakic POAG, with very few intraoperative and no postoperative complications.
Intravitreal anti‐vascular endothelial growth factor therapy for acute ROP: our management of ten eyes
Authors: Barillà Donatella , Guagliano Rosanna , Bertone Chiara , Montescani Silvia , Arpa Cristina , Quaranta Luciano
Published: December 2019

Purpose

To report our experience in the management of ten eyes with acute Retinopathy of Prematurity (ROP) after intravitreal (i.v.) Anti‐vascular Endothelial Growth Factor (anti‐VEGF) treatment.

Methods

A retrospective study was performed in 122 infants screened for ROP over a two year period. Among the 122 premature infants, five (ten eyes), affected by zone 1‐2 type 1 ROP stage II‐III, were selected and treated with an intravitreal injection of Ranibizumab (0.25 mg/0.025 ml). The mean gestational age of the infants was 25 weeks and the mean birth weight 616 g. The treatment was performed at approximately 35 weeks post menstrual age (PMA). At each follow‐up visit, we performed fundus examination with indirect ophthalmoscopy and RetCam III. Fundus photographs and fluorescein angiography (FA) were taken using RetCam III, pre‐treatment and 1 month after treatment. FA was repeated if necessary.

Results

Two months after treatment, FA showed a reactivation of ROP in four eyes in which we had performed laser photocoagulation. In two eyes FA follow up showed zone 2 angiographic abnormalities that were also laser treated. In the other four eyes vascularisation showed improvement even if the extreme peripheral retina was not fully vascularised, in these cases we decided just to observe. After a follow up of at least six months, the final retinal outcome was assessed. In the six laser treated eyes, laser scars were evident, without any sign of disease reactivation. In the four eyes which were only treated by i.v., we observed the permanence of an avascular zone in the extreme periphery without signs of disease activity.

Conclusions

We experienced that anti‐VEGF treatment allows retinal vascularisation to further progress towards the peripheral retina, so that less laser treatment in the case of ROP progression or reoccurrence is needed. Anti‐VEGF is effective therapy to reach anatomical and functional outcomes, in zone 1‐2 type 1 ROP cases.
Biological tissue as a active substances drug prolonged diffusion support
Authors: Grossetete Florine , Barnouin Laurence
Published: December 2019

Objective

Use of ground proceed umbilical cord lining (Wharton Jelly) for an prolonged diffusion of active substance with a progressive disintegration of the tissue within few days.

Methods

Ground proceed umbilical cord lining is a tissue that contains proteoglycans, TGFß, elastin, and collagen. By calibrating the grinding and associating a freeze‐drying with a second desiccation at 35°C‐ 50 microBar, fibers are sticking together and enable having a compact and shaped final product. The addition of solution of gentamycin sulfate in the ground gelatinous tissue is performed before the step of freeze‐drying.Titrations of gentamycin in the solution of ground tissues before and after freeze‐drying are performed according to the method A from European Pharmacopeia.

Results

Titration of gentamycin mixed with ground tissues is from an average of 3024 UI/sample (SD 94) before freeze‐drying. After freeze‐drying: 2997 UI/sample (SD:189). This titration is the one expected regarding the solution preparation, so there is no loss of active principle activity. Titration in time submitted to mechanical and hydration stress are in progress.

Discussion

Tissues extracted from Wharton Jelly are products used for different pathologies of ocular surface. The use of a solid form, shaped at convenience can enable diffusion of active substance drug to treat more complex infections of the ocular surface and also in eye chambers.
Corneal refractive surgery and the risk of retinal detachment
Authors: Kanclerz Piotr , Grzybowski Andrzej
Published: December 2019

Purpose

Corneal refractive surgery (CRS) is an elective procedure presenting a low risk of complications. Nevertheless, as commonly eyes with perfect best corrected visual acuity are treated, sight‐threatening complications are a major concern. The aim of this study was to evaluate the association between corneal refractive surgery and the risk for developing retinal detachment (RD).

Methodology

PubMed and Web of Science were the main resources used to search the medical literature search.

Results

Presumed mechanisms by which CRS would induce RD include biomechanical changes caused by the suction ring, excimer laser shock wave or the use of femtosecond laser. However, the reported RD rates after CRS were similar to those of an unoperated myopic cohort. We found no differences between RD rates in laser in situ keratomileusis and superficial CRSs. The pooled analysis found an overall risk of developing RD after laser in situ keratomileusis of 0.08% (95% CI: 0.69%–0.82%). Higher preoperative refractive error, older patients age and male sex were associated with an increased risk of developing RD after CRS.

Conclusions

The current analysis presents no convincing evidence supporting the association between CRS and increased risk for developing RD. Patients at risk of developing RD should be treated with caution and informed that CRS reduces the refractive error, but does not eliminate the risks related to myopia.
Afro‐Caribbean patients have a lower disc vascular density than European patients: a cross‐sectional study
Authors: Liseth Salazar Quiñones Maria , Sheng Lim K. , Yu‐Wai‐Man Cynthia , De Antonio Ramirez Alba , García Feijoo Julián , Dora Méndez Hernánez Carmen , Peña Urbina Pilar
Published: December 2019

Purpose

To determine if there are racial differences in disc vascular density between Afro‐Caribbean and European patients, and the relationship with disease severity in glaucoma.

Design

Cross‐sectional study.

Participants

50 eyes from 32 Afro‐Caribbean glaucoma patients, 35 eyes from 22 European glaucoma patients, 23 eyes from 14 Afro‐Caribbean normal controls, 24 eyes from 12 European normal controls.

Methods

All patients underwent a complete ophthalmic examination. Disc vascular density was measured using OCT angiography. We compared the disc vascular density of Optic head nerve and peripapillary between Afro‐Caribbean and European patients in normal controls and glaucoma patients. We evaluate superficial vascular complex and matched the severity of glaucoma between the two groups using mean deviation from Humphrey visual field 24‐2 test. We also performed Spearman correlation between the disc vascular density and mean deviation, visual acuity, intraocular pressures, central corneal thickness and cup‐disc ratio.

Main Outcome Measures

Disc vascular density.

Results

Afro‐Caribbean normal controls had a lower mean disc vascular density (42.4 ± 0.8 [SEM]) than European normal controls (46.2 ± 0.2; p < 0.0001). We matched the severity of visual field loss in 32 eyes from Afro‐Caribbean glaucoma patients (MD = 5.97 ± 0.75) and 32 eyes from European glaucoma patients (MD = 4.17 ± 0.73; p = 0.090). Afro‐Caribbean glaucoma patients also had a lower mean disc vascular density (33.26 ± 6.60 [SEM]) than European glaucoma patients (36.68 ± 5.28; p = 0.022). There was a moderate correlation between disc vascular density and mean deviation (r = −0.70, p < 0.0001) in the Afro‐Caribbean glaucoma patients. We found no correlation between disc vascular density and mean deviation (r = −0.31, p = 0.070) in the European glaucoma patients.

Conclusions

Afro‐Caribbean patients have lower disc vascular density than European patients in normal controls but not subgroup mild, moderate or advanced glaucoma.
TelCaps in retinal vascular diseases: an overview
Authors: Paques Michel
Published: December 2019

Telangiectatic capillaries (TelCaps), also termed capillary macroaneurysms, are commonly observed in retinal vascular diseases and may cause chronic macular edema even if distally located. Their recognition is important since their targeted photocoagulation may be clinically beneficial. Diagnosis of TelCaps is facilitated by the use of indocyanine green angiography, particularly in its late frames, since they appear to be a correlation between ICG staining and the intensity of blood –retinal barrier breakdown. This is a crucial point, since TelCaps often escape fundus and OCT examination. As such, the identification of TelCaps may contribute to a reevaluation of chronic macular edema management. Here we will discuss this emerging concept, and its integration into management schemes of chronic macular edema, especially for diabetic macular edema. A randomized study is currently ongoing in France, aiming at investigating the potential of targeted photocoagulation to reduce the amount of intravitreal injections.
Optical coherence tomography biomarkers for idiopathic epiretinal membrane after pars plana vitrectomy
Authors: Chatziralli Irini
Published: December 2019

Idiopathic epiretinal membrane (iERM) refers to fibroglial cellular proliferation at the vitreoretinal interface, above the internal limiting membrane (ILM) mainly at the macular area. The gold standard for the treatment of iERM is pars plana vitrectomy (PPV), which provides good anatomical and functional results. However, some patients did not exhibit visual acuity improvement after PPV for iERM. Advances in optical coherence tomography (OCT) have led to the introduction of new anatomic measures, such as precise evaluation of individual layers, qualitative and quantitative assessment of fluid distribution, inner retinal irregularity, ellipsoid zone integrity and disorganization of inner retinal layers (DRIL), which may predict more accurately the treatment success or failure after treatment. The purpose of this lecture is to investigate if characteristics identified on OCT may serve as biomarkers to predict postoperative visual outcomes in patients with iERM treated with PPV.
De novo missense variants in WDR37 cause a severe ocular syndrome
Authors: Semina Elena
Published: December 2019

Using exome sequencing we have discovered de novo missense variants in WDR37 in unrelated patients with a complex phenotype, which we named WDR37 syndrome. Patients with this syndrome demonstrated corneal opacity, coloboma and microcornea, dysmorphic facial features, significant neurological impairment with structural brain defects and seizure onset shortly after birth, poor feeding, and variable skeletal, cardiac, genitourinary defects and early lethality in one. WDR37 encodes a protein of unknown function with seven predicted WD40 domains. We undertook further functional characterization of the gene and variants in human cell lines and zebrafish. Immunocytochemistry and Western blot studies revealed that wild‐type WDR37 is predominantly localized in the cytoplasm and mutant proteins showed similar expression levels and localization. CRISPR‐Cas9 mediated genome editing generated zebrafish mutants with missense and frameshift variants, including one that replicated a human variant. Zebrafish carrying heterozygous missense mutations demonstrated larval lethality, while embryos with frameshift alleles survived to adulthood, suggesting a dominant negative mechanism for the human missense variants. Analysis of RNAseq data from mutant zebrafish embryos revealed significant upregulation of cholesterol biosynthesis pathways. Additional studies into possible function of this important factor and disease mechanisms are ongoing. In summary, we report a novel human disease gene with an essential role in vertebrate development and provide the first insight into its possible role.
The fish scale based Biocornea: an off‐the shelf device for managing acute corneal perforations
Authors: Schuitmaker Hans
Published: December 2019

The fish scale based ologen™ Biocornea is developed as an alternative to the temporary cadaveric corneas that do not meet all the criteria of transplantation grade tissue. Such temporary corneas (so‐called “0‐cornea”) can be used to patch a perforated, lacerated or ulcerated cornea for hours up to a few days, until a suitable donor cornea is procured for transplantation. The temporary cornea ensures integrity of the eye globe, maintaining inner eye structures and intraocular pressure so that other eye structures are not damaged while the patient waits for donor tissue. However, a 0‐cornea is not always available and for these circumstances the fish scale based Biocornea offers an alternative way to close the eye for a limited period of time to preserve the globe, until a human donor cornea is available. The Biocornea implant is composed of decellularized fish scales that have been acquired from a certified fish processing plant operating according to the EU Food Safety Management System. Initially, these ologen™ Biocorneas were tested for the intended purpose in a pig transplantation model. The favorable outcome of these experiments forms the basis for a “first in man” clinical trial which now runs in Cologne and Bochum in Germany as part of the ARREST BLINDNESS project. The experience obtained from the clinical trial will be the basis for further development of new prototype Biocorneas.
Pain and sensation in dry eye disease
Authors: Gallar Juana
Published: December 2019

The recent definition of dry eye disease (DED) proposed by DEWS II includes, for the first time, neurosensory abnormalities in etiology of the disease. In DED, reduced tear secretion leads to inflammation and corneal nerve damage, which induce sensitization of corneal polymodal and mechano‐nociceptors, and an abnormal activity of cold thermoreceptors thus evoking pain and eye dryness sensations. Moreover, long‐term nerve damage and inflammation, modify the expression of ion channels involved in the stimulus detection (transduction) and excitability of ocular sensory neurons, changing their impulse firing and their connectivity at the CNS, which is the basis of neuropathic pain and dysesthesia referred to the eye surface in DED patients. These altered transducing and encoding ion channels are potential molecular targets to modulate neuropathic nerve activity in DED, currently under study. Although many subjective (surveys and questionnaires, corneal sensitivity measurement) and objective metrics (morphology and density of subbasal corneal nerves and immune cells, blink parameters, biomarkers in tears) are currently used to evaluate pain in DED patients, new instruments and procedures designed to obtain more reliable information on eye sensations and pain in DED need to be developed (SAF‐2017‐83674‐C2‐1‐R and 2‐R, Agencia Estatal de Investigación‐ERDF, Spain‐EU, and PROMETEO/2018/114, Generalitat Valenciana, Spain).
Biomechanical profile of refractive surgery procedures
Authors: Balidis Miltos
Published: December 2019

The impact of corneal biomechanics continues to be increasingly recognized as an integral part of refractive surgery outcomes. Corneal biomechanical properties are of major importance in laser refractive surgery and must be taken into consideration to reduce the risk for iatrogenic ectasia. Some in vivo corneal biomechanical alterations are possible to quantify with ORA and Corvist ST but are difficult to interpret and use in clinical practice due to their dependence of IOP, CCT, refractive status, time from surgery and age. Development and refinement are needed if ORA and Corvis ST should be implemented in a screening procedure of the biomechanical strength before refractive surgery.

Flap‐creation technique plays a major role in changing the biomechanical stability of the cornea. Nevertheless several studies suggest that the type of procedure is not as important as the native charac‐teristics of the patient’s cornea in determining the risk for ectasia. Although we may have reached a plateau of technological improvement in excimer laser tissue ablation, the introduction of small incision lenticule extraction (ReLEx SMILE), has changed the face of corneal refractive surgery in particular in its effect on corneal biomechanics. Mathematical analysis and finite‐element models suggest that SMILE may preserve corneal biomechanical properties better than LASIK. Furthermore, the current in vivo studies performed with ORA and Corvis ST indicate that SMILE is equal or superior to LASIK in terms of preservation of the postoperative biomechanical strength.

However CH and CRF were reduced after refractive surgery but no differ‐ences were found between SMILE and flap‐based (FLEx and FS‐LASIK) refractive surgeries in the RCTs. Studies have demonstrated that in LASIK and PRK, the amount of refractive error corrected is related to the changes in corneal biomechanical properties. Considerable reduction in the corneal biomechanical properties observed even in ‘flap‐less’ procedures like PRK and SMILE,

Brillouin microscopy provides safe and non contact method for measuring longitudinal elastic modulus of ocular tissues. It provides three‐dimensional resolution of the imaged tissue revealing spatial variations in mechanical properties. Its clinical usefulness has already been demonstrated in corneal diagnostic and treatment monitoring and may eventually be a valuable tool for surgical planning of refractive and therapeutic procedures.

question both in vivo and ex vivo, and by mathematical or finite‐element models of the cornea
Accommodative intraocular lens concepts
Authors: Eppig Timo
Published: December 2019

The restoration of accommodation still remains the biggest challenge of cataract surgery. The desire for real pseudophakic accommodation remains unchanged although modern multifocal lenses provide acceptable presbyopic correction and visual quality. Numerous concepts for accommodative intraocular lenses have been presented during the last decades but none of these were as successful as multifocal lenses are today. These concepts can be divided into three principles: Optic shift moves a single lens or a set of lenses along the optical axis such as the, for example, the 1CU (HumanOptics), the Crystalens (Bausch & Lomb) and the Synchrony (Visiogen/AMO). Varying radius of curvature changes refraction oft he lens such as, for example, the Juvene (LensGen). Replacement of the or refilling of the capular bag remains an interesting option but refilling has not reached the stage of human clinical trials. We will present an overview on the various concepts for the restoration of accommodation in the pseudophakic eye and the current clinical status.
Significance of ocular signs of monoclonal gammopathy
Authors: Szentmary Nora
Published: December 2019

Monoclonal gammopathy of undetermined significance (MGUS), solitary bone plasmocytoma, Waldenström’s disease (macroglobulinaema) and asymptomatic or symptomatic multiple myeloma are all different stages of the same disease, all with monoclonal gammopathy. Up‐to date there are no data on ocular signs of monoclonal gammopathy , especially concerning corneal signs, in the literature.

Our aim was to examine the ophthalmic signs of monoclonal gammopathy.

Patients of the South‐Pest Hospital Center – National Institute for Infectology and Haematology, Department of Hematology and Stem Cell Transplantation, with monoclonal gammopathy, were enrolled in our study. Beside detailed ophthalmic and slit‐lamp examination, haematological history and blood counts were recorded and analysed.

Fifty‐five patients were examined (17 male, 38 female, age 68±9.6 years). We observed corneal immunoglobulin deposition in 4 (7.28%), dry eye disease in 18 (32.75%), cataract in 28 (50.9%), epiretinal membrane in 4 (7.27%), glaucoma in 3 (5.45%), and a stage following central retinal artery occlusion in 1 patient (1.81%). 10 patients (20%) underwent cataract surgery prior enrollment, 7 of them (12,72%) had surgery on both eyes. Monoclonal gammopathy was related to IgG heavy chains in 41 (74.5%), IgA in 13 (23.5%) and IgM in 1 patient (1.81%) and concerning light chains, kappa‐chain was dominant in 35 (63.6%) and lambda in 20 patients (36.3%).

Due to the relative high prevalence of dry eye disease and cataract in patients with monoclonal gammopathy, we recommend regular ophthalmological checkup of these patients. The occurrence of corneal deposits is relative uncommon (7,28%) in monoclonal gammopathy.
Pathogenesis of idiopathic epiretinal membrane
Authors: Kontou Evgenia
Published: December 2019

To describe the pathophysiological events involved in the formation and progression of epiretinal membranes (ERMs).

Epidemiologic studies have found a clear relationship between ERM formation, ageing, and posterior vitreous detachment. Increased prevalence of ERM is noted in the population older than 60 years, with peak prevalence between 70 and 79 years. Histologic studies of surgically obtained ERM specimens identified cellular and extracellular matrix components. A key element in ERM formation and its progression toward a contractile membrane is the transdifferentiation of those cellular components toward myofibroblasts. ERMs stiffness is a result of the proportion between its collagenous and non‐collagenous elements. Additionally, modifications of membrane macromolecules, such as accumulation of advanced glycation end products, which constitutes an age‐related phenomenon, may increase stiffness of the membrane and contribute to the fibrotic process.

Retinal membranes have been described for more than 150 years and comprise the most common type of fibrocellular proliferation found at the vitreoretinal interface. Although patients with ERM can be asymptomatic when the membrane is thin and translucent, its progression to a thick, and contractile membrane may result in macular distortion, inducing metamorphopsia and loss of visual function. Understanding disease pathogenesis is essential in order to develop appropriate therapeutic approaches.
OCT Angiography ‐ A new tool to assess vascular autoregulation in the retina
Authors: Garhöfer Gerhard
Published: December 2019

Vascular autoregulation is defined as the ability of a vascular bed to keep blood flow constant despite changes in ocular perfusion pressure. In the eye, the retinal circulation and also to a certain degree the choroidal circulation exhibit autoregulatory properties in response to changes in blood or intraocular pressure. Interestingly, it has been shown that these autoregulatory properties are compromised in ocular diseases such as glaucoma or diabetic retinopathy. New tools such as OCT angiography allow now for the investigation of vascular changes up to the microvascular level. The current talk will summaries how these new technologies can be used to get more insight in the complex regulation of blood flow in the eye.
Definition and diagnosis of Dry Eye Disease (DED)
Authors: Messmer Elisabeth M.
Published: December 2019

According to the Dry Eye Workshop (DEWS) II report, Dry eye is defined as ‘a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles’. Diagnosing DED includes triaging questions, an analysis of risk factors, symptom evaluation using questionnaires, and diagnostic testing for homeostasis markers. These include non‐invasive tear film break up time for tear film stability, tear film osmolarity and ocular surface staining. For specific treatment recommendations, hyperevaporative DED and aqueous deficient DED must be differentiated by meibomian gland and tear lipid evaluation as well as tear volume assessment.
Novel therapies for Bestrophinopathies
Authors: Carr Amanda‐Jayne
Published: December 2019

Bestrophinopathies are a group of clinically distinct diseases caused by mutations in Bestrophin1 (BEST1). BEST1 is expressed exclusively in the retinal pigment epithelial (RPE) cells of the eye, where it functions as an ion channel. Mutations in the BEST1 gene affect the function of the RPE leading to the death of overlying retinal cells and subsequent vision loss.

The dominant and recessive nature of Bestrophinopathies may necessitate different approaches to prevent or ameliorate these diseases. Potential therapeutic options for Bestrophinopathies focus on restoring correct gene expression, though viral gene therapy and gene editing, or by targeting nonsense mutations through translational readthrough‐inducing drugs. We are using induced pluripotent stem‐derived RPE created from patients with Bestrophinopathies to investigate these potential therapies in vitro.
Mutation in the mouse histone gene Hist2h3c1 leads to degeneration of the lens vesicle and severe microphthalmia
Authors: Graw Jochen
Published: December 2019

During an ENU (N‐ethyl‐N‐nitrosourea) mutagenesis screen, we observed a dominant small‐eye mutant mouse with viable homozygotes (gene symbol Aey69). We determined linkage to mouse chromosome 3 between the markers D3Mit188 and D3Mit11; sequencing demonstrated a 358A‐>C mutation (Ile120Leu) in the Hist2h3c1 gene and a 71T‐>C (Val24Ala) mutation in the Gja8 gene. Analysis of eye development in the homozygous mutants documented an altered lens development starting from the lens vesicle stage including decreasing expression of crystallins and of lens‐specific transcription factors PITX3 and FOXE3. In contrast, we observed an early expression of retinal progenitor cells characterized by BRN3 and OTX2. These changes in the retina happen in parallel with apoptotic processes in the lens vesicle. The excessive retinal hyperproliferation is characterized by an increased level of Ki67. At postnatal stages, all principal retinal cell types are present, when the overgrowing retina fills the entire bulbus. Morpholino‐mediated knock‐down of the hist2h3ca1 gene in zebrafish leads to a specific perturbation of lens development. When injected into zebrafish zygotes, only the mutant mouse mRNA leads to severe malformations (cyclopia to microphthalmia). The wild‐type Hist2h3c1 mRNA can rescue the morpholino‐induced defects corroborating its specific function in lens development. The data highlight the importance of Hist2h3c1 (encoding a canonical H3.2 variant) in the formation of lens and retina.
Autoantibodies and eye movement disorders
Authors: Robert Matthieu
Published: December 2019

Introduction

New auto‐antibodies seem to be discovered every month and the field of eye movement disorders is fully part of the game: anti‐GAD, GM1, GQ1b, Hu, Ri, etc. What are their specificity? their practical use at the bedside? where and how to ask for their dosage? what to they tell us of their associated conditions?

Objective

To answer these questions in a synthetic way.

Methods

Literature review using Pubmed and Google Scholar; chosen clinical cases.

Results

Various oculomotor presentations should prompt auto‐antibodies dosage: oculogyric crises associated with tics or chorea; progressive saccadic intrusions with associated ataxia, typically evolving into opsoclonus‐myoclonus syndrome; acquired neurological nystagmus with no obvious explanation, and non‐compressive unexplained ophthalmoparesis, especially when associated with unremarkable MRI ‐ or with MRI showing mild signs of encephalitis. The targets of these antibodies can be: the central nervous system, the peripheral nervous system, the neuromuscular junction or the extraocular muscles. Relevant auto‐antibodies can be classified into: antibodies directed against intracellular neuronal proteins, responsible for paraneoplastic neurological syndromes (Hu, Yo, Ri, CV2, amphiphysin, Ma1, Ma2) and antibodies directed against neural surface or synaptic antigens, responsible for autoimmune encephalitis syndromes, most frequent in children (AMPA, CASPR2, GABAR, GAD, GD1a, GD1b, GM1, GQ1b, GT1a, LGI1, NMDA).

Conclusions

Auto‐antibodies are often the clue of ‘impossible’ oculomotor cases. They should be dosed in chosen and rare situations with specific techniques; the results should be interpreted according to the known specificity of each auto‐antibody.