bluuebunny/crossref_metadata_2025 huggingface dataset:
Dexamethasone intravitreal implant (Ozurdex) in phakic patients with diabetic macular oedema resistant to anti‐VEGF therapy: Short‐term visual and anatomical outcomes in a real‐world study
Authors: Thulasidharan Suresh , Walker Lawrence , Rennie Christina , Krishnan Radhika
Published: January 2024

Aims/Purpose: To prospectively study and analyse the clinical effectiveness of using intravitreal dexamethasone (IVO) implant in treatment resistant phakic patients with centre involving diabetic macular oedema (DMO).

Methods: Prospective interventional case series of phakic patients with persistent centre‐involving diabetic macular oedema, who received an IVO implant between May 2022 and February 2023 were included. Primary outcome measures include best corrected visual acuity (BCVA) and central retinal thickness (CRT) at baseline, 2 months and 6 months. Secondary efficacy outcome measures include, change in level of cataract and change in intraocular pressure (IOP) control requiring topical treatment or interventional procedures.

Results: Nine eyes from eight patients were included. Mean age at treatment was 61.87 ± 11.07 years with male preponderance (8:1). There was no statistically significant difference in BCVA at baseline compared to 2 months following IVO (0.291 ± 0.185 vs. 0.287 ± 0.208, respectively, p = 0.919) or comparing BCVA at baseline to BCVA 6 months following IVO (0.291 ± 0.185 vs. 0.347 ± 0.153, respectively, p = 0.063). Reduction in CRT from baseline to 2 months following IVO was highly significant (436.4 ± 65.1 vs. 305.9 ± 58.6, respectively, p = 0.006) and reduction in CRT comparing baseline and 6 months following IVO which remained significant (436.4 ± 65.1 vs. 363.2 ± 96.1, p = 0.041). Mean intraocular pressures was raised in 44.4% eyes with medical management required in 33.3%. Recurrence of maculopathy was noted in 88.9% eyes. Cataract requiring surgery was performed in one eye.

Conclusions: This prospective series shows that phakic patients, with persistent DMO following anti‐VEGF therapy undergoing IVO, resulted in a highly statistically significant reduction in CRT at 2 months following IVO which was maintained at 6 months (p = 0.04) although there is high recurrence. BCVA remains stable over the 6‐month period with no statistically significant change.
Remodelling of the lamina cribrosa thickness in proliferative diabetic retinopathy as a pathogenetic factor of retrolaminar migration of silicone oil after vitrectomy
Authors: Karliychuk Maryna , Pinchuk Serhii , Urazov Artem
Published: January 2024

Aims/Purpose: to analyse the relationship of lamina cribrosa (LC) thickness in patients with proliferative diabetic retinopathy (PDR) after vitrectomy with SiO tamponade with retrolaminar migration of intraocular silicone oil (SiO).

Methods: This retrospective study included 35 patients with PDR after vitrectomy with SiO tamponade who underwent unenhanced head computed tomography for various clinical indications. All images were visually evaluated for subretinal and retrolaminar migration of SiO involving the anterior visual pathway (optic nerve, optic chiasm, and optic tract) and the ventricular system. LC thickness was measured with spectral domain optical coherent tomography (SD OCT) using LC_Thickness_programm.m and main_low_noise_filters_programm.m, based on the adaptive compensation algorithm for eliminating a high‐level noise in the deep layers of optic nerve and improving the visualization of the LC posterior border, as well as for processing B‐scan with a set of 3 digital filters: Butterworth Low‐pass Filter inverion image, Wavelet Low‐pass Filter Analysis Daubechies original and inversion image.

Results: In our patients with PDR the average LC thickness was 697 ± 35 μm (589 to 768 μm), that was 1.9 times higher than in healthy people (p < 0.001). We detected subretinal and retrolaminar silicone oil migration in 10 of the 35 patients (28.57%), noting silicone oil at the optic nerve head (n = 2), retrolaminar optic nerve (n = 4), optic chiasm (n = 2), optic tract (n = 1) and in the lateral ventricles (n = 3). 3 patients had migration to 2 locations each (1 – in retrolaminar optic nerve and optic chiasm, 2 – in retrolaminar optic nerve and lateral ventricle). We compared the LC thickness of patients without and with subretinal and retrolaminar SiO migration. It was established that LC thickness of patients with subretinal and retrolaminar SiO migration was significantly less (589 to 658 μm) than in patients without SiO migration (673 to 768 μm). It should be noted that the number of cases positive for migration was small, limiting the statistical power and accuracy of the prevalence.

Conclusions: A direct correlation between scleral LC thickness and retrolaminar migration of SiO in patients with PDR after vitrectomy with SiO tamponade was revealed.
An unusual case of bilateral type 1 idiopathic macular telangiectasia
Authors: Haddar Selim , Braham Imene Zhioua , Mrad Syrine Ben , Hachicha Ines , Erraies Khalil , Mili Ilhem , Zhioua Raja Gmar
Published: January 2024

Purpose: To report an unusual case of Type 1A idiopathic macular telangiectasia (IMT).

Methods: A single case presentation.

Results: A 54‐year‐old female presented with gradual vision loss in both eyes. Best‐corrected visual acuity (BCVA) was limited to counting fingers in both eyes. Fundus examination showed bilateral hard macular exudates associated with small macular telangiectasia. Fluorescein angiography (FA) revealed early bilateral macular punctuated hyperfluorescence corresponding to macular telangiectasia. Macular swept‐source optical coherence tomography (SS‐OCT) showed bilateral cystoid macular oedema associated with serous retinal detachment. OCT‐angiography (OCT‐A) showed clearly some of the perifoveal aneurysmal dilations and telangiectasia. Based on these findings, the patient was diagnosed with bilateral type 1A IMT according to Gass and Blodi classification and was treated with intravitreal anti‐vascular endothelial growth factor (anti‐VEGF) injections. Three months later, SS‐OCT revealed partial regression of the exudative signs and BCVA improvement.

Conclusions: We described a case of a bilateral Type 1A IMT, affecting a middle‐aged woman, without peripheral involvement. Usually, this entity is unilateral and evolving the mid periphery. Macular SS‐OCT helped to visualize the extent of retinal involvement in the presence of masking macular hard exudates. OCT‐A visualized some of the telangiectasias however, compared to FA, some vascular abnormalities were undetectable, probably due to a turbulent or low blood flow. Treatment with intravitreal Anti‐VEGF can lead to incomplete response.
Optical coherence tomography angiography findings after silicone oil tamponade for rhegmatogenous retinal detachment
Authors: Braham Imene Zhioua , Boubaker Cyrine , Mokrani Manel , Hachicha Ines , Mili Ilhem , Boukari Mejdi , Zhioua Raja Gmar
Published: January 2024

Aim: To describe retinal structural and microvascular changes using Swept source optical coherence tomography (SS‐OCT) and OCT angiography (OCT‐A) in patients with rhegmatogenous retinal detachment (RRD) treated by vitrectomy (PPV) and silicone oil (SO) tamponade and to identify the final visual acuity (VA) prognostic factors.

Methods: In this retrospective study, patients were treated with PPV and SO tamponade for uncomplicated DRR. After SO removal, retinal thickness was assessed by SS‐OCT. The foveal avascular zone (FAZ) area, the fractal dimension (FD), the lacunarity (LAC) and the macular capillary vessel density (VD) in the superficial (PCS) and deep plexuses (PCP) and in the choriocapillaris (CC) were analysed.

Results: Thirty‐one eyes were included in this study; 20 eyes (65%) had macula ‘OFF’ RRD. The mean post‐operative final VA was 3.2/10. Outer retinal defect was observed in 74.1% of the operated eyes. Central macular thickness (CMT) and parafoveal thickness were significantly decreased compared with healthy fellow eyes (p = 0.048; p = 0.029). Outer nuclear layer (ONL) and subfoveal choroid were significantly thinned in the operated eyes (p = 0.003; p = 0.017). The FAZ in PCS and PCP and was larger (p = 0.042; p = 0.032), the VD (total, parafoveal and parafoveal) in the PCP were significantly lower (p = 0.004; p = 0.012; p = 0.049) and the lacunarity (LAC) at the PCP level was significantly higher (p = 0.040) in the operated eyes than in the fellow eyes. The final VA was correlated with the defect of the outer retina (p < 0.002) and the VD in PCP (p = 0.0199). The duration of SO tamponade was signifcantly correlated with the outer retinal defect (p = 0.011), the enlargement of FAZ area (p = 0.001) and the VD in DCP (p = 0.002).

Conclusion: SIO can lead to structural and vascular retinal ischaemic defect such as enlargement and irregularity of the FAZ and predominant PCP capillary abnormalities. These changes could reflect vascular hypoperfusion in eyes with SO tamponade and may represent a potential cause of retinal thinning and unexplained visual loss.
Study of the metallome and transcriptome of a degenerating cellular model of the retinal pigment epithelium
Authors: Álvarez Lydia , Alvarez‐Barrios Ana , García Montserrat , Pereiro Rosario , Gonzalez‐Iglesias Hector
Published: January 2024

Aims/Purpose: To study the changes on the metallome and transcriptome of a cellular model of the retinal pigment epithelium (RPE) during its in vitro degeneration after 4 months in culture.

Methods: Primary cultures of human fetal RPE cells were established in P12 transwell inserts and cultured for 4 months. Cell pigmentation and barrier function was followed up using optical microscopy and measurement of the transepithelial electrical resistance (TEER). Samples were collected at 21, 91 and 133 days in culture and analysed for gene expression, metal homeostasis of Ca, Na, P, Mg and P, and extracellular deposit formation through RNA sequencing (RNA‐Seq), elemental mass spectrometry (ICP‐MS) and immunocytochemistry assays, respectively.

Results: RPE cells formed a differentiated monolayer at 21 days in culture, expressing specific genes and proteins of RPE and giving increasing TEER values. However, after 133 days in culture, loss of tight junction proteins (i.e. CLDN19 and BEST1) and electrical resistance was seen, together with loss of pigmentation and increase of apolipoprotein E deposition in the extracellular space. Gene expression analysis showed an enrichment on apoptotic processes, biomolecule phosphorylation, and signs of epithelial‐to‐mesenchymal transition (EMT). Degeneration of RPE cells concurred with an increase of Na and P content in the cytosol and decrease of Mg, while a decrease of Mg, P and Cu was determined in the insoluble fraction of cells. Time‐dependent changes of metals were accompanied with the alteration of metal transporters and antioxidant enzymes using metals as cofactors.

Conclusions: Degeneration of RPE cells in culture was characterized by depigmentation of cells, improper barrier function, downregulation of antioxidant protection, loss of epithelial phenotype, and changes on the levels of Na, P, Mg and Cu, as well as of the expression of their homeostatic proteins.
Geographic atrophy (GA) secondary to AMD: Online medical education can significantly improve ophthalmologists' knowledge and confidence on evidence‐based guidance for patient management
Authors: Trier Siggi , Carpenter Kate , Reid Karen , Lanzetta Paolo , Schmidt‐Erfurth Ursula , Kodijkian Laurent
Published: January 2024

Aims/Purpose: To determine if online medical education for ophthalmologists (Ophth) could improve knowledge for GA disease impact, patient assessment and confidence in emerging therapies.

Methods: Ophth participated in an online 30 min video, 3 expert roundtable discussion with accompanying slides. A repeated pairs pre−/post‐assessment study design was used, assessing three multiple choice knowledge and one confidence question. Statistical significance tests: McNemar's test for individual questions (5% significance level, p < 0.05), paired sample t‐test for overall average correct responses and confidence rating; data collected 16 December 2022 to 22 March 2023. Test completers: 230.

Results: At baseline, 3% Ophth answered all three questions correctly, increasing to 37% (p < 0.01) post‐assessment. 58% Ophth reported improved confidence understanding the rationale for targeting the complement system with GA therapies. The activity significantly increased knowledge on impact of GA on time to loss of ability to drive (pre: 7%, post: 52%, p < 0.001), on recall of detrimental lesion characteristics (pre: 40%, post: 67% p < 0.01) as well as capability of automated OCT analysis algorithms to predict GA progression (pre: 51%, post: 69%, p < 0.001). Only 24% Ophth polled currently document >75% patients with advanced atrophic AMD with OCT/FAF imaging.

Conclusions: Online medical education in the form of expert roundtable discussions with accompanying slides can significantly improve knowledge on assessing patients with GA using imaging, understand the rationale to treat and increase confidence in understanding the role of complement inhibition. Polling showed a lack in documenting patients for GA progression. Complementary education is warranted during the introduction of a novel therapeutic horizon in GA management in clinical practice to support evidence‐based patient selection guidance for emerging therapies.
Effect of phospholipid‐eluting contact lens on dry eye in rabbit
Authors: Park Sehie , Hwang Jin Sun , Oh Sun Hee , Shin Young Joo
Published: January 2024

Aims/Purpose: To investigate the effects of new phosphatidylcholine‐eluting contact lenses (PC‐CL) on dry eye in Rabbit.

Methods: 18 New Zealand rabbits were used in this study. Meibomian gland orifices were electrocauterized in the dry eye group. PC‐CL were provided from Neo Vision (Yongin, Korea). Rabbits were fitted with control contact lens on one eye and 0.1% PC‐CL on the other eye or with 0.1% PC‐CL on one eye and 0.3% PC‐CL on the other eye. Tear break‐up time (TBUT), tear osmolarity, and corneal fluorescein staining score (FSS), central corneal thickness (CCT), and conjunctival histology were evaluated.

Results: In both dry eye and non‐dry eye group, TBUT was longer and tear osmolarity was lower in 0.1% PC‐CL compared to control lens. Cornea was stained with fluorescein in dry eye group, but not in non‐dry eye group. CCT showed no difference in PC‐CL and control lens on both dry eye and non‐dry eye group. In dry eye group, goblet cell density tended to be slightly higher in PC‐CL compared to control. There was no significant difference in TBUT, tear osmolarity, CCT, FSS, and goblet cell density between 0.1% PC‐CL and 0.3% PC‐CL.

Conclusions: PC‐CL stabilized tear film and lowered tear osmolarity in dry eye. Thus, it may reduce dry eye symptoms and contact lens complications in clinical practice.
Quantitative comparison of in vivo and ex vivo meibography in BALB/c mice
Authors: Yoon Youngchae , Hwang Ho Sik
Published: January 2024

Aims/Purpose: We recently introduced a new method for in vivo meibography in BALB/c mice. In this study, we compared the in vivo and ex vivo meibography in young and old mice.

Methods: Eighteen male BALB/c mice (9 young mice and 9 old mice) were used in this study. We performed in vivo meibography on the upper and lower eyelids of the mice. Then, the mice were sacrificed, and the eyelids were excised en bloc. Ex vivo meibography was performed on the eyelids. For quantitative comparison, the number of meibomian glands(MG) identifiable in in vivo and ex vivo meibography was counted. For the same MG in lower eyelids of in vivo and ex vivo meibography, the horizontal length(HL), vertical length(VL), and area of the MG were measured and compared using image J.

Results: The number of mean identifiable MG of in vivo and ex vivo meibography was 7.4 ± 0.8 and 11.6 ± 0.6 in upper eyelids (p < 0.001), and 8.4 ± 0.7 and 11.8 ± 0.9 in lower eyelids (p < 0.001), respectively. The mean HL of the same MG of in vivo and ex vivo meibography was 0.16 ± 0.03 and 0.17 ± 0.03 mm (p = 0.001). The mean VL of the same MG of in vivo and ex vivo meibography was 0.59 ± 0.08 and 0.69 ± 0.09 mm (p = 0.001). The mean area of the same MG of in vivo and ex vivo meibography was 0.14 ± 0.05 and 0.17 ± 0.05 mm2 (p = 0.001). The HL (r = 0.929, p < 0.001), VL (r = 0.737, p < 0.001), and area (r = 0.777, p < 0.001) of a MG of in vivo and ex vivo showed a strong positive correlation between them. The in vivo/ex vivo ratios of HL, VL, and area was 0.92 ± 0.09, 0.82 ± 0.05, and 0.82 ± 0.23 in young mice, and 0.95 ± 0.06, 0.89 ± 0.10, and 0.82 ± 0.16 in old mice. They showed no significant difference between young and old mice (p = 0.404, 0.102, and 0.984, respectively).

Conclusions: This is the first study to compare quantitatively in vivo and ex vivo meibography in mice, the most common animal models for dry eye syndrome. In vivo meibography showed shorter HL, VL, and smaller area compared to ex vivo meibography, but there was a strong positive correlation between them. Because there was no significant difference in the in vivo/ex vivo ratio of HL, VL, and area between young and old mice, there is no problem comparing in vivo meibography between young and old mice.

Reference

Hwang HS et al. A novel transillumination meibography device for in vivo imaging of mouse meibomian glands. Ocul Surf. 2021 Jan;19:201–209.
Cold plasma treatment for fungal keratitis
Authors: Trosan Peter , Reif‐Eberhard Anselm , Nadermann Freya , Staehlke Susanne , Warnke Philipp , Fuchsluger Thomas
Published: January 2024

Aims/Purpose: Fungal keratitis is serious ocular infection caused by any of the fungi species. It is treated with antifungal medications, in worst scenario with cornea transplantation. The therapy is still challenging due to poor drug penetration into the cornea. Cold plasma, produced by ionization of argon gas, contains especially reactive species but also UV radiation which damage microorganisms. The aim of this study is to determine the effect of cold plasma on human corneal epithelial cells (HCE), corneal tissue and multiple pathogen microorganisms to assess the opportunity of cold plasma treatment for fungal keratitis.

Methods: The effect of cold plasma on HCE was analysed by the light microscopy, Live/Dead assay, metabolic activity assay, and immunohistochemistry. Disinfecting potential was analysed by plating prevalent yeasts (Candida albicans, C. krusei, C. parapsilosis, C. glabrata) on agar plates and treated with cold plasma. Plasma treatment of infected human donor corneas with C. albicans was determined by measurement of O.D. of liquid culture.

Results: The treatment of HCE by cold plasma led to the change of the morphology, significantly lower viability, metabolic activity and proliferation of the cells. Yeast strains were significantly eradicated completely after 5 min of cold plasma treatment (p ≤ 0.001). Cold plasma therapy of the infected human donor corneas showed the decrease of the infection in all tested time intervals with statistical significance (p ≤ 0.01, p < 0.05 and p ≤ 0.001 respectively for 1, 2 and 5 min treatment).

Conclusions: Cold plasma treatment showed negative impact on the culture of HCE. The analysis of its effect on the whole corneal tissue is in progress. On the contrary, a significant reduction of CFU was observed in all examined Candida spp. and significant decrease of infection was determined in infected corneas. Therefore, the cold plasma technology showed a potential to be an effective treatment for fungal keratitis.
Epidemiological profil of post contusive hyphaema experience of the paediatric ophthalmology department of Casablanca
Authors: Ayad Rima , Ghizlane Daghouj , Hammoumi Zineb , El harrar Assia , Ajdour Lamiaa
Published: January 2024

Aims/Purpose: Hyphaema is defined as the presence of blood in the anterior chamber. It occurs after a contusive or perforating ocular trauma or in the aftermath of ocular surgery. The aim of our work is to analyse the clinical, therapeutic and evolutionary profile of post‐contusive hyphaema.

Methods: A retrospective study was conducted on 66 children (33 eyes) admitted to the ophthalmologic emergency room for post‐contusive hyphaema followed and treated in the paediatric ophthalmology department of the 20 August hospital in Casablanca between January 2015 and January 2023.

Results: There was a male predominance with 67% of boys affected. The average age was 9.5 years. The main cause of consultation was visual acuity (VA) loss in 49%. On examination, the initial VA was <1/10 in 38% of cases, the ocular tone was >20 in 30% of cases. Hyphaema was classified as stage I in 26.4%, stage II in 52%, stage III in 15.2%, stage IV in 6.4%. Post‐traumatic cataract was present in 50% of the cases, lens dislocation in 22% of the cases, angle recession in 6%. Intravitreal haemorrhage was present in 2 patients, berlin oedema in 3 patients. The treatment prescribed in all patients was strict rest, abundant drinks, oral and local corticotherapy and dilatation with atropine. In addition, a hypotonizing treatment was prescribed for the patients who presented an ocular hypertonia. The evolution was marked by the total resorption of the hyphaema in 90% of the cases. Surgical treatment (hyphaema lavage) in 10% of cases. The final VA was >6/10 in 60% of cases. The most serious complication was haematocornea in 6% of cases.

Conclusions: Frequent and serious condition in children that can jeopardize the functional prognosis of the eye. When the diagnosis is made, the management must be early in order to avoid complications.
Analysis of epithelial corneal layer after phacoemulsification
Authors: Cerdà‐Ibáñez Marta , Peris‐Martínez Cristina
Published: January 2024

Aims/Purpose: To verify whether changes occur in the epithelial corneal layer after phacoemulsification depending on the number of endothelial cells.

Methods: This is a prospective observational study on patients who were going to have cataract removal surgery. The patients were divided into two groups in accordance with their endothelial cell count: one group with more than 1500 endothelial cells and the other with fewer than 1500 cells. We analysed the epithelial layer with the RTVue (Optovue, Fremon, USA) device. The epithelial mapping was performed before surgery, the day after the intervention, a week after the procedure, 1 and 6 months post‐surgery.

Results: The epithelial layer was greater in patients who had more than 1500 endothelial cells. This difference was statistically significant at every visit except the day after surgery, when there were no differences between the groups.

Conclusions: Immediate postoperative corneal oedema following phacoemulsification affects the cornea irregularly at the sublayer level. Corneal oedema secondary to the cataract removal surgery can affect the epithelial layer, but this is a transient change since a week after surgery this layer showed the same differences as before the procedure. These changes were encountered in the central cornea, without involvement of the incision sites. Patients with fewer endothelial cells showed a lower epithelial layer thickness even though there were no significant statistical differences in pachymetry between the two groups. Possibly this difference is secondary to a higher stromal thickness layer to compensate for such changes.
Feasibility of 3D bioprinting of a corneal stroma tissue equivalent using a desktop 3D printer
Authors: Diafa Aspasia , Tsouknidas Alexandros
Published: January 2024

Aims/Purpose: The aim of this poster is to present a proof of concept for the possibility of three‐dimensional bioprinting of a corneal stroma equivalent, using a modified (open source) three‐dimensional desktop printer.

Methods: We present the experimental process designed for the realization of the three‐dimensional bioprinting of a corneal stroma equivalent, utilizing a tissue‐specific deposition nozzle based on commercially available and easily printable parts. The final design considers all the required modifications of the 3D printer and the selection of the appropriate bioink.

Results: We designed a prototype proprietary device to be fitted on a MendelMax 3 3D printer. The particular open‐source device works as a syringe extruder, with the syringe containing the bioink. The composition of the bioink is based on a carefully selected blend of collagen, alginate, and keratocytes. The mixture demonstrates suitable structural integrity and transparency after crosslinking.

Conclusions: This proof‐of‐concept work demonstrates that, with proper modification, a standard commercial three‐dimensional printer can be modified to use bioinks and bioprint corneal stroma tissue equivalents. More research is required regarding the viability of the tissue equivalents and their clinical applications.
Ocular pathogens and antibiotic susceptibility patterns in bacterial keratitis during 2010–2019 in the county of Östergötland, Sweden, a retrospective study
Authors: Roth Jenny , Toprak Baris , Somajo Sofia , Macedo Antonio Filipe , Lagali Neil
Published: January 2024

Aim/Purpose: The aim of this study was to identify causative bacterial species, aetiology of infection and determine antibiotic susceptibility in bacterial keratitis in the county of Östergötland, Sweden.

Methods: We performed a retrospective search in the regional Electronic Health Record, period 2010–2019, for patients diagnosed with keratitis according to the codes of the International Classification of Disease.

Results: One‐hundred and ninety patients with lab culture‐confirmed bacterial keratitis were included in the final analysis. Antimicrobial susceptibility tests were available for all confirmed bacterial keratitis. Laboratory tests revealed a total of 188 (84%) Gram‐positive and 36 (16%) Gram‐negative pathogens. The most frequently reported bacterial species were coagulase‐negative staphylococci (CoNS) (39%), Staphylococcus aureus (17%) and Cutibacterium acnes (10%). Pseudomonas spp. was the most frequently reported Gram‐negative bacterial species (7%). Contact lens wear and severely ill/blind eye were the top two aetiological factors associated with bacterial keratitis. Most of the isolates (157 out of 173) were reported susceptible to first line antibiotics, which are fluoroquinolones, and nearly all (145 out of 155) isolates were susceptible to chloramphenicol ‐ that is the recommended treatment in combination with fluoroquinolones. We did not detect any cases of methicillin‐resistant Staphylococcus aureus. The type of treatment and the outcome of the treatment including visual acuity were assessed in the cohort.

Conclusions: Our results revealed a positive rate of bacterial keratitis of 59% for the samples sent to the laboratory. The bacterial species causing keratitis in the current study were consistent over time and the species were susceptible to the recommended antibiotics. These findings indicate patients are receiving the correct treatment.
Artificial tears, preservatives, so what?
Authors: Alnoor Umalbaninn , Ahrensberg Simone , Freiberg Josefine , Kolko Miriam , Nagstrup Anne , Heegaard Steffen
Published: January 2024

Aims/Purpose: To investigate the cell survival of human conjunctival goblet cells (CGs) when incubated with preserved and preservative‐free (PF) artificial tears (AT) used against dry eye disease (DED). The following ATs were tested: 0.011% benzalkonium chloride (BAK)‐preserved Viskøse® Øjendråber, 0.006% BAK‐preserved Oftagel®, 0.005% BAK‐preserved Oculac®, 0.001% PolyQuad™‐preserved Systane® Ultra, 0.01% Cetrimide‐preserved Artelac®, and PF ATs: Systane® Ultra, Oculac®, Oftagel®, and Thealoz® Duo.

Methods: Primary cultures of human conjunctival CGs were cultivated from donor conjunctiva. After incubation with the above‐mentioned ATs for 2 h, CG survival was analysed using a lactate dehydrogenase assay and calculated to a negative control.

Results: AT preserved with 0.011% BAK reduced GC survival by 28% compared to negative control (p = 0.001). The remaining ATs did not significantly alter the cell survival.

Conclusions: BAK‐preserved ATs cause GC death in a concentration‐dependent manner. Reduction of the GC density may contribute to development of DED. PF‐ATs and PolyQuad‐ and Cetrimide‐preserved ATs may thus be a better choice for treating DED than BAK preserved ATs, as the latter may add to the ocular surface disease.
Preparation and outcome of swollen versus dextran deswollen grafts in descemet membrane endothelial keratoplasty (DMEK)
Authors: Zwingelberg Sarah
Published: January 2024

Aims/Purpose: To evaluate the influence of organ culture medium containing dextran on graft characteristics during preparation as well as the outcome of subsequent Descemet Membrane Endothelial Keratoplasty (DMEK).

Methods: 31 corneoscleral rims of the Eye Bank of the University Hospital of Cologne with a donor age between 52 and 74 years were examined between 2018 and 2022 for their intraoperative preparation conditions and the outcome after performing 31 DMEKs. For this purpose, corneoscleral rims were randomized into two organ‐cultured groups, one immersed in culture medium with dextran (group A, n = 16) and the other in medium without dextran (group B, n = 15). The intraoperative graft preparation conditions were noted by using a standardized scoresheet, including splitting and stripping behaviour, central and peripheral attachment as well as graft fragility. The post‐operative outcome parameters were defined as Best Spectacle‐Corrected Visual Acuity (BSCVA), central and peripheral corneal thickness (CCT and PCT), endothelial cell count (ECC) and re‐bubbling rate.

Results: In both groups, all 31 DM‐endothelium grafts were usable for DMEK. There was no significant difference in the intraoperative preparation conditions of swollen versus dextran deswollen DM‐endothelium grafts in respect to stripping (p = 0.722) and to Descemet membrane splitting behaviour (p = 0.013). The fragility of the grafts showed no significant difference (p = 0.433), as well as the peripheral scars indicating a pseudophakic donor (p = 1.000) and the tendency for central tearing (p = 0.484) during preparation. No significant difference in the outcome 12 months after DMEK in conditions of swollen versus dextran deswollen DM‐endothelium grafts regrading CCT (p = 0.189), re‐bubbling (p = 0.704), PCT (p = 0.063), could be observed. BSCVA was significantly better in group B 12 months after DMEK with p = 0.032 (group A 0.08 ± 0.38: group B 0.03 ± 0.13).

Conclusions: This pilot study does not show relevant and significant differences between swollen versus dextran deswollen grafts in DMEK transplantation. Future prospective studies with higher patient numbers are needed. Our study suggests also non‐deswollen donors as suitable for DMEK surgery.
Long‐term results and persistence of topical cyclosporine a 0.1% treatment in patients with dry eye disease in a tertiary eye centre
Authors: Aghayeva Fidan , Assaf Abdelrahman , Lanzl Ines
Published: January 2024

Aims/Purpose: This study aims to assess clinical effectiveness, outcome and safety of long‐term topical Cyclosporine A 0.1% Cationic Emulsion (CsA 0.1% CE; Ikervis®) treatment in patients with dry eye disease.

Methods: Retrospective chart review of 55 patients (110 eyes) with dry eye disease and severe keratitis treated with Ikervis® since 2016 for at least 12 months without interruption was performed. Study outcomes were median change from baseline in corneal fluorescein staining (CFS, Oxford Grade Scale) score, clinical outcome, treatment discontinuation reason, ocular symptom severity and adverse events (AEs) during long follow‐up.

Results: The mean age of patients was 65.96 ± 1.9 years, 81.8% women and 18.2% men. The mean follow‐up was 33.8 ± 19.1 (12–80) months. 43.6% eyes had grade III of CFS at baseline and 4.5% had grade I of CFS at the last follow up. The median CFS score reduced from 2 (1–3) at baseline to 0 (0–1) at the last follow up and this reduction was statistically significant (p < 0.001) from the fourth week. Clinical outcome was defined as active/worsening in 1.8%, stabilization in 14.5%, improvement in 69.1% and resolution in 14.5% of the cases. 65.5% of the patients have continued the treatment without interruption during the whole follow‐up, the treatment discontinuation in 35.5% of the cases were due to improvement (14.5%), AEs (5.5%), patient decision (5.5%), treatment failure (3.6%), other reason (5.5%). Ocular symptom severity was significantly reduced from baseline during the follow up (p < 0.001). In 27.3% cases treatment‐related AEs were reported, most of them (64.7%) were mild.

Conclusions: This study shows a long‐term clinical effectiveness and persistence of the topical CsA 0.1% CE treatment in patients with dry eye disease. The significantly reduction of the dry eye symptoms severity from the fourth week of the initiated Ikervis® treatment sustains for a long follow up, and thus definitely improves the quality of life of patients.

Reference

1. Geerling G, Hamada S, Trocmé S, Ræder S, Chen X, Fassari C, Lanzl I; PERSPECTIVE study group. Real‐World Effectiveness, Tolerability and Safety of Cyclosporine A 0.1% Cationic Emulsion in Severe Keratitis and Dry Eye Treatment. Ophthalmol Ther 2022; 11(3): 1101–1117. doi: 10.1007/s40123‐022‐00487‐x.
Higher occurrence of ocular surface disease symptoms in patients with atopic dermatitis—Data in the FOREVER study
Authors: Hansen Pernille May , Rovelt Jens , Tolstrup Jette , Thyssen Jacob P. , Heegaard Steffen , Kolko Miriam
Published: January 2024

Aims/Purpose: Atopic Dermatitis (AD) is a common inflammatory skin disease that often begins in early childhood and may continue into adulthood. AD severity, and comorbid bronchial asthma and rhinitis have been associated with increased prevalence of Ocular Surface Diseases (OSD) in AD patients (1). OSD is common in the general population and symptoms from the ocular surface do not always lead to examination and diagnosis by healthcare professionals. The purpose of this study was to investigate the occurrence of self‐reported symptoms from the ocular surface in AD patients compared to the population without AD.

Methods: A questionnaire study was conducted as a part of project FOREVER (Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability) to examine the relationship between eye and overall health in Danish citizens. Symptoms related to the ocular surface included tearing, blurred vision, red, itching, burning, gritty, and dry eyes. Logistic regression models were used to investigate associations between AD and the occurrence of symptoms related to the ocular surface.

Results: 36874 people had completed the FOREVER questionnaire. 797, 3305 and 32 772 participants answered that they have current AD, previously had AD, and never had AD, respectively. 69% (550/797) and 67% (2201/3305) in the group with current AD and previous AD experienced one or more ocular surface symptoms compared to 60% (19 517/32 772) in the non‐AD group. The odds ratio of AD and ocular surface symptoms was 1.27 [1.09–1.48] (p < 0.01) and 1.17 [1.08–1.26] (p < 0.001) for current and previous AD when adjusting for age, sex, smoking status, and atopic comorbidities; bronchial asthma and rhinitis.

Conclusions: Our study found that participants with AD from the FOREVER cohort reported a higher occurrence of OSD symptoms compared to participants who have never suffered from AD. This suggest that AD patients are at higher risk of developing OSD symptoms.

Reference

1. Rønnstad ATM, Hansen PM, Halling AS, et al. Factors associated with ocular surface disease and severity in adults with atopic dermatitis: a nationwide survey. J Eur Acad Dermatol Venereol. 2022;36(4):592–601.
Investigation of apoptotic and inflammatory markers in hypoxia induced human cornea epithelial cells co‐cultured with limbal mesenchymal stem cells
Authors: Canbulat Zehra , Aydemir Ayse Dilara , Hasanreisoğlu Murat
Published: January 2024

Aims/Purpose: Here we aim to investigate the effect of hypoxic conditions (5% O2) on human cornea epithelial cells (HCECs) and also by creating a system in which limbal mesenchymal stem cells (LMSCs) are co‐cultured with HCECs, the effect of LMSC is examined on this subject via paracrine mechanism.

Methods: HCECs are either mono‐cultured or co‐cultured with LMSC under hypoxic and normoxic (%21 O2) conditions. HCECs of after 6, 24, and 48 h of incubation were harvested for comprehension of changes in RNA and protein expression levels. Bcl2, Bax, Erk1/2 protein levels are checked through western blot analysis, whereas expression levels of cytokines, which are IL‐6, IL‐8, IL‐10 and TGF‐β1, are investigated via RT‐qPCR.

Results: Both anti‐inflammatory and pro‐inflammatory cytokine gene expression levels in co‐cultured model increased upon hypoxia and normoxia conditions compared to cytokines in mono cultured HCECs. In addition to the increase in cytokine levels in the co‐culture condition, this increase is less in the hypoxia exposed co‐culture in comparison to the normoxic co‐culture model. Furthermore, anti‐ and pro‐apoptotic protein expression levels have significantly changed upon co‐cultured both in normoxia and hypoxia conditions.

Conclusions: In conclusion, it is observed that hypoxia with co‐cultured model decreased inflammation and acted as crucial role in cell death mechanism. These results were further confirmed with apoptotic protein ratio in hypoxic co‐cultured cells. The underlying mechanism will be examined in future experiments.
An attempt to evaluate the anterior surface homeostasis in patients with diabetic retinopathy
Authors: Kuligowska Agnieszka , Pius‐Sadowska Ewa , Machaliński Bogusław , Machalińska Anna
Published: January 2024

Aims/Purpose: The aim of our study was to verify the presence of dry eye disease (DED) in diabetic patients. We also tried to determine the relationship between diabetic neuropathy and the presence of ocular surface disease.

Methods: 52 type 2 diabetic patients and 52 non‐diabetic, sex and age‐matched controls were included in the study. All participants completed the OSDI questionnaire and undergone the eye surface examination with IDRA analyser including interferometry, tear meniscus height, non‐invasive tear break‐up time (NIBUT), evaluation of blepharitis, blinking pattern, pupillometry and meibography. Corneal sensation in the centre of the cornea and its 4 quadrants was analysed with the Cochet–Bonnet aesthesiometer (CBE). Corneal confocal microscopy images of sub‐basal plexus were evaluated using ACCMetrics. The concentrations of the neurotrophic factors: beta‐NGF, BDNF, NT‐4 as well as inflammatory mediators (TNF‐α, VEGF, IL‐2, ‐1β, ‐4, ‐5, ‐6, ‐8, ‐10, ‐12, GM‐CSF, IFN‐γ) were measured in the tear film using Luminex 200 analytic platform.

Results: The OSDI was significantly higher in diabetic patients compared to the controls (mean: 29.08 vs. 11.67 points; p < 0.001). The groups did not differ in the results of the Schirmer test, interferometry, NIBUT and meibography values. Moreover, we did not find the elevation in the concentrations of the ocular surface inflammation indicators in tears of diabetics as compared to controls. There was a significant difference in tear meniscus between groups. Diabetics achieved significantly worse results than the control group in terms of corneal sensation, innervation parameters (average nerve length = 6.70 vs 11.54 mm/mm2; p < 0.001, average density = 9.26 vs. 19.19/mm2; p < 0.001), scotopic pupillometry and blinking interval. Tear film BDNF concentrations were lower in diabetic eyes as compared to controls (mean 1.85 vs. 2.29 pg/mg; p = <0.001).

Conclusions: The lack of proinflammatory response in diabetic eyes and no differences between groups in the terms of objective clinical features may suggest that there is no cause‐and‐effect relationship between diabetes and DED. Corneal innervation disorders, clinically noticeable as decreased corneal sensation, result in a number of complications, that have a direct impact on the subjective feelings of the patient.
Comparative analysis of corneal parameters between DMEK and UT‐DSAEK eyes in 3‐year follow‐up
Authors: Machalińska Anna , Kuligowska Agnieszka , Kuśmierz‐Wojtasik Monika
Published: January 2024

Aims/Purpose: The aim of the study was to provide a comparative analysis of corneal parameter changes compared to their preoperative values between Descemet membrane endothelial keratoplasty (DMEK) and ultrathin Descemet stripping automated endothelial keratoplasty (UT‐DSAEK) patients.

Methods: The study included 27 eyes after UT‐DSAEK and 34 eyes after DMEK. Best corrected visual acuity (BCVA), endothelial cell count (ECC), central corneal thickness (CCT), mean keratometry (MK), mean astigmatism (MA), astigmatism asymmetry (AA) and higher order aberrations (HOAs) were assessed at baseline and 1, 3, 6, 12, 24 and 36 months after the surgery.

Results: Patients after DMEK had significantly better BCVA than patients after UT‐DSAEK (mean 0.9 vs. 0.6 at 24th month, respectively, p = 0.002 and 0.9 vs. 0.7 at 36th month of follow‐up, respectively, p = 0.001). From the 3rd month post operation, ECC was higher in the DMEK eyes than in the UT‐DSAEK eyes (p = 0.01). However, the groups did not differ in this parameter at 24th and 36th month of observation. In a bivariate analysis that was adjusted for age, DMEK was associated with a smaller decrease in posterior MK at the 1‐month (β = −0.49, p = 0.002), 3‐month (β = −0.50, p < 0.001), 6‐month (β = −0.58, p < 0.001) and 12‐month (β = −0.49, p < 0.001) follow‐up visits. Significant differences in MK, AA and HOA values of the posterior surface of the cornea at 12th, 24th and 36th month of observation and MA of the posterior surface of the cornea at 24th month of observation were found as well, with no differences in the total values of these parameters. Accordingly, no significant differences in changes in MA, AA or HOAs compared to the baseline values were identified between the eyes after DMEK and UT‐DSAEK at any follow‐up time point.

Conclusions: UT‐DSAEK seem to be an easier and safer technique than DMEK while maintaining similar outcomes regarding irregular astigmatism and total keratometry values. Nevertheless, DMEK produces significantly better BCVA outcomes.
Change in posterior astigmatism with degree of decentring graft in patients with descemet stripping automated endothelial keratoplasty
Authors: Park Jae Hyun , Kim Hyun‐Seung
Published: January 2024

Aims/Purpose: Aligning the center of grafts in patients with Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) is difficult but important process. We investigated how the graft centring affected posterior astigmatism in patients.

Methods: This study analysed 63 patients (63 eyes) who received DSAEK. Postoperative posterior astigmatism of patients was measured using pentacam, and the decentring of the graft was measured by using the distance between the patient's optic centre and the centre of the graft. Correlation analysis was performed on the relationship between graft decentring and posterior astigmatism. In addition, the spherical aberration of the cornea before and after surgery was analysed and investigated.

Results: The average posterior astigmatism of the patients before surgery was 1.70 ± 2.25, and the average posterior astigmatism was 0.66D ± 0.43, confirming a decrease in posterior astigmatism after surgery (p < 0.05). The mean decentring of graft was 0.45 ± 0.33 mm. Preoperative spherical aberration was 0.192 ± 0.53 and postoperative spherical aberration was 0.044 ± 0.37, and these differences were not statistically significant (p > 0.05). Analysis of the relationship between graft decentring and postoperative posterior astigmatism showed no statistically significant correlation (p > 0.05).

Conclusions: In this study, no significant correlation was found between centring of the graft and posterior astigmatism after surgery. However, centring of the graft in DSAEK plays an important role in graft survival and postoperative prognosis, surgeons should pay attention to centring well during surgery.
Anti‐inflammatory effect of mulberry anthocyanins on experimental dry eye
Authors: Lee Ji Young , Kwon Jin Woo
Published: January 2024

Aims/Purpose: To investigate the anti‐inflammatory effects of mulberry anthocyanin on dry eye.

Methods: HME‐DDS (Hot‐Melt Extrusion‐Drug Delivery System) was used to maximize the content of anthocyanin in mulberry. Experimental dry eye (EDE) was induced by topical 0.2% BAK (benzalkonium chloride) eye drops instilled twice a day for 1 week. The animals were randomly divided into those treated with and without the mulberry HME‐DDS products (10 g/kg/day). Ocular surface staining using fluorescein and Schirmer's test were performed. After 2 weeks of treatments, the animals were sacrificed, and tissues were harvested, and immunohistochemistry was performed to detect inflammatory response to compare with the control group.

Results: After mulberry HME‐DDS treatments, the corneal staining score was significantly decreased compared to the untreated group (3.33 ± 0.83, 7.63 ± 1.00; p = 0.004). In addition, mulberry HME‐DDS treated group showed a significant increase in tear production compared with the untreated group (8.83 ± 2.29, 6.18 ± 2.44; p = 0.014). The mulberry HME‐DDS products decreased the expression of IL‐1, IL‐6 and IL‐17 in the cornea and lacrimal gland.

Conclusions: Mulberry with HME‐DDS technology improved ocular surface findings and tear production. In addition, the mulberry HME‐DDS product reduced the expression of inflammatory cytokines in the cornea and lacrimal gland, and it was speculated that anthocyanins containing mulberry could improve clinical manifestations by suppressing inflammation.
Characterization of the proteome changes in an in vitro hyperosmotic dry eye model employing human corneal epithelial cells
Authors: Lin Hao , Manicam Caroline , Pfeiffer Norbert , Grus Franz , Perumal Natarajan
Published: January 2024

Aims/Purpose: The detrimental effects of tear hyperosmolarity on human corneal epithelial (HCE) cells is a primary cause of dry eye syndrome (DES). However, the molecular mechanisms underlying inflammatory processes and cellular dysfunction in HCE are largely unknown. This study characterized the proteome changes in an optimized hyperosmolarity‐induced DES model in vitro.

Methods: An in vitro hyperosmolar (400–550 mOsm) DES model was established in a simian virus 40 (SV40)‐immortalized HCE cell line. Cells incubated in medium with physiological osmolarity (312 mOsm) were used as control. Cell viability, cell death and intracellular reactive oxygen species (ROS) levels were analysed with MTS, Annexin‐V‐FLUOS, crystal violet and DCFDA assays. Mass spectrometry‐based proteomics analyses characterized the proteome and elucidated the underlying molecular changes.

Results: The HCE cell viability was significantly decreased in a concentration‐dependent manner with increasing hyperosmolarity compared to control at 48 hr (450 mOsm, −47%, p = 2.7 × 10−8; 500 mOsm, −71%, p = 1.1 × 10−4; 550 mOsm, −84%, p = 2.6 × 10−5). Notably, cell adherence was significantly decreased (p = 5.8 × 10−9), while levels of ROS (p = 3.6 × 10−2) and apoptosis (p = 3.6 × 10−2) were significantly increased at 450 mOsm compared to control. Proteomics analysis identified ~2000 proteins (FDR <1%) and, as many as 215 proteins were found to be significantly (p < 0.05) differentially abundant in the 450 vs. 312 mOsm. The effects of high hyperosmolarity (450 mOsm)‐induced damage resembling DES on the HCE cell were further demonstrated by the expression of proteins involved in the activation of inflammatory response (p = 5.5 × 10−3), apoptosis (p = 5.3 × 10−4) and generation of ROS (e.g., glutathione S‐transferase P) (p = 7.1 × 10−3). Moreover, many differentially expressed proteins were also implicated in the regulation of cell viability (p = 1.1 × 10−6) and organization of cytoplasm (e.g., cyclase associated actin cytoskeleton regulatory protein 1) (p = 2.4 × 10−2).

Conclusions: In summary, an optimized hyperosmolarity‐induced DES cell culture model for proteomics analysis was established, and specific alterations in the proteome were characterized in this model. This in vitro model would be instrumental for testing therapeutic targets for DES in the future.