bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of new biomaterials with amniotic membrane growth factors in corneal regeneration in vivo
Authors: Garmendia Ayla Basasoro , Reparaz Iraia , Esporrín‐Ubieto David , Nunes Juliana , Mendicute Javier , Fernandez María Mercedes , Dupin Damien , Calderón Marcelo , Diaz Aitor , Acera Arantxa
Published: December 2022

Purpose: To compare the effect on corneal healing of two novel hydrogels releasing proteins obtained from amniotic membrane (AM).

Methods: Forty‐four New Zealand White rabbits underwent corneal wounding with NAOH 1 M and received different treatments: Control (group 1), AM transplantation (group 2), model A hydrogel (group 3) and model B hydrogel (group 4). The progression of wound healing was recorded with photographs and assessed by measuring the remaining epithelial defect over time. Histology was performed to examine acute and chronic changes.

Results: There were no statistically significant differences between groups in epithelial defect areas (mm2) at days 0, 7, 14, 21 and 28. The percentage of wound closure (%) showed statistically significant differences on day 7 between Group 1 and Group 4 (p = 0.03). The percentage of completely healed corneas showed no statistically significant differences between the control and treated groups on days 14, 21 and 28, but on day 7, there were differences between Group 4 and Control (p = 0.02). On days 14 and 21 the rate of completely healed corneas was higher in Group 3 and Group 4 (55% on day 14 and 30% on day 21) compared to Group 1 (44.4% on day 14 and 11.1% on day 21).

Conclusions: The novel biodegradable hydrogels with AM proteins could promote corneal re‐epithelialization. The chosen animal model showed a high rate of wound reopening once closed. Group 4 hydrogels showed low adhesiveness so the implant movement and the fragile regenerated epithelium could justify the higher de‐epithelized areas on day 7. The results show a higher number of wounds with complete epithelialization and a smaller epithelial defect area (mm2) in the treated groups compared to control, even after removal of the AM proteins, which might indicate that proteins secreted in the early stages of epithelialization could enhance corneal wound closure.
Oxygen metabolic retinal function in retinitis pigmentosa correlates with disease severity
Authors: Zabek Olga Maria , Calzetti Giacomo , Prétot Dominique , Scholl Hendrik Peter Nicolas , Volpe Maria della
Published: December 2022

Purpose: The aim of our study was to evaluate retinal function with white light dark‐adapted full‐field sensitivity threshold (FST) and find possible correlations with metabolic function measured with retinal oximetry (RO) in patients with retinitis pigmentosa (RP).

Methods: In this prospective observational study (BASEC 2020–00122), FST and RO measurements were performed on 66 RP eyes (33 subjects, 12♀ 21♂) aged between 18 and 80 years (mean 43.2 years); all eyes were graded for disease severity. Main outcome parameters were white FST thresholds using the Diagnosys Espion system with the ColorDomeTM LED full‐field stimulator (Diagnosys LLC, Lowell, MA) as well as the main RO parameters: the mean arterial (A‐SO2; %), venular (V‐SO2; %) oxygen saturation, their difference (A‐V SO2; %), and the corresponding mean diameters of the peripapillary retinal arterioles (D‐A; μm) and venules (D‐V; μm) recorded with the oxygen saturation tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems UG, Jena, Germany). In addition, semi‐automated kinetic perimetry (V4e, III4e, I4e, III3e isopters, Octopus 900®, Haag‐Streit AG Bern, Switzerland) was performed and included in the linear mixed‐effects models analysis calculated with SPSS®.

Results: Neither the oxygen saturation parameters (p > 0.21) nor the D‐A and D‐V (p > 0.13) showed significant correlations with the FST. However, when compared systematically with the visual field (VF) areas of the different isopters, RO parameters V‐SO2 (p = 0.024) and A‐V SO2 (p < 0.02) showed significant correlations. Furthermore, both V‐SO2 and A‐V SO2 showed gradual changes with more pronounced impairment in oxygen metabolic function in advanced stages of RP when analysed in subgroups of disease severity grades.

Conclusions: In advanced stages of RP, RO showed a significant association with standardized VF testing parameters and presented with gradual changes of more pronounced impairment in retinal oxygen metabolic function. Unlike standardized VF parameters, white dark‐adapted FST does not appear to correlate with retinal oxygen metabolic function in RP patients, implying that the two examinations may capture unrelated aspects of the retinal pathological process.
Comparison of two primary intraocular lymphoma experimental murine models
Authors: Skrlova Eva , Uherkova Eva , Malarikova Diana , Klimova Aneta , Svozilkova Petra , Kesa Peter , Matous Petr , Herynek Vit , Kucera Tomas , Klener Pavel , Heissigerova Jarmila
Published: December 2022

Purpose: The research on experimental models of primary intraocular lymphoma (PIOL) helps to elucidate pathophysiology of the disease and to find new therapeutical strategies. The purpose of the project was to compare characteristics of two experimental murine models of PIOL.

Methods: PIOL was induced in immunocompetent mice by intravitreal injection of syngeneic DLBCL cell suspension. For mice strain C3H/Hen cell line 38C13 was used, for BALB/CaNn it was cell line A20. Following the injection mice were monitored clinically 2 times per week. The experiment was terminated at first signs of exophthalmos or on day 30. Eyes were collected post mortem and histologically processed.

Results: Both mice strains show high percentage (above 80%) of PIOL development. Disease progression is faster in C3H/HeN with exophthalmos occurring in all mice no later than day 21, on average on day 11. Vitreous involvement is a predominant sign in the clinical presentation of this group. In BALB/CaNn mice exophthalmos occurs on average on day 22. At the same time, tumorous infiltration of retina, tumorous infiltration of optic disc and tumorous retinal detachment are dominant signs. The difference in development of exophthalmos is most probably due to different affinity of cancer cells for orbital tissue.

Conclusions: PIOL has slower progression in BALB/CaNn strain with later or no occurrence of exophthalmos. Varying time of exophthalmos development is most probably due to difference between the affinity of 38C13 and A20 cells for orbital tissue. The primary affinity of the 38C13 cell line for orbital tissue can explain earlier development of exophthalmos in C3H/HeN mice. This and the fact that the PIOL progression is slower in BALB/CaNn strain predisposes the latter to be more suitable for therapeutic experiments planned in the future.

Financial support of this project: AZV MZ CR NU20‐03‐00253, SVV UK 260516.
The relationship between outdoor exposure and myopia on university students, measured by conjunctival ultraviolet autofluorescence (CUVAF)
Authors: Recalde Sergio , Bilbao Valentina , Hernandez Maria , Gonzalez‐Zamora Jorge , De la Puente Miriam , Escriche Elena , Ruiz Pablo , Bezunartea Jaione , Mariezkurrena Ainara , Alonso Elena , de Viteri Manuel Saenz , Barrio Jesús , Layana Alfredo García , Fernandez‐Robredo Patricia
Published: December 2022

Purpose: The purpose of this study was to analyse whether outdoor (OD) exposure could exert a protective effect against the development of myopia and HM, in two different cohorts of university students that differ in the time of OD activities in their study programs. Moreover, CUVAF, as an objective measure of time spent outdoors, was also investigated in this cohort.

Methods: A cross‐sectional observational study was carried out using two different cohorts of students, one of medical students (MS) and the other of environmental science students (ESS). All participants underwent an automatic objective refraction, axial length measurement, colour fundus photographs, and CUVAF area (BAF module on the Heidelberg Spectralis HRA + OCT). All the participants filled out a questionnaire of life style and myopia history. For all statistical analyses, corrected p values < 0.05 (two‐tailed) were considered statistically significant using SPSS 20.1 Software.

Results: A total of 208 participants were recruited, 156 were MS and 52 were ESS. The data showed that 66.66% of the MS were myopic versus only 50% of the ESS (p = 0.021; OR 95 = 2.03 (95% CI 1.1–3.6). With regards to OD activities, ESS spent significantly more hours per week doing OD activities than MS (p < 0.0001), but with respect to near work activities, there was no significant difference between both cohorts. In this sense, it was found that high myopia MS spent significantly fewer hours outdoors than their controls (p < 0.05). The degree of myopia was inversely associated with CUVAF in all university students, and a statistically significant positive correlation was observed between spherical equivalent and CUVAF (r = 0.248 [95% CI 0.094–0.390]; p = 0.001).

Conclusions: The results showed that OD activities could reduce the onset and progression of myopia not only in children, but also in young adults. In addition, CUVAF represents an objective, non‐invasive biomarker of OD exposure that is inversely associated with myopia, and can be useful to follow‐up myopic patients.
Raloxifene induced keratopathy: A case report
Authors: Sim Haeun , Jeong Jeonga , Kang Min Ji , Hwang Jehyung
Published: December 2022

Purpose: We report a case of corneal verticillata in a patient who had been taking raloxifene for a prolonged period. To our knowledge, this is the first case report of an ocular side effect of raloxifene.

Methods: Case presentation.

Results: A 69‐year‐old female patient presented to our clinic for her routine eye check‐up. On slit‐lamp examination, whorl‐like subepithelial deposits were observed in the bilateral corneas. She was diagnosed with corneal verticillata (vortex keratopathy) caused by raloxifene. A follow‐up evaluation was conducted after discontinuation of the drug; however, the corneal opacity did not improve.

Conclusions: Patients with corneal verticillata should be asked regarding any intake of raloxifene for osteoporosis, as it may cause corneal verticillata.

References

1. Martinkovich S, Shah D, Planey SL, Arnott JA. Selective oestrogen receptor modulators: tissue specificity and clinical utility. Clin Interv Ageing 2014;9:1437–1452. doi: 10.2147/CIA.S66690.

2. Muehlbacher M, Tripal P, Roas F, Kornhuber J. Identification of drugs inducing phospholipidosis by novel in vitro data. ChemMedChem 2012;7(11):1925–1934. doi: 10.1002/cmdc.201200306.

3. Michaud M, Mauhin W, Belmatoug N, et al. When and how to diagnose Fabry disease in clinical pratice. Am J Med Sci 2020;360(6):641–649. doi: 10.1016/j.amjms.2020.07.011.

4. Zinchuk O, Watanabe M, Hayashi N, Fukushima A, Ueno H. A case of tamoxifen keratopathy. Arch Ophthalmol 2006;124(7):1046–1048. doi: 10.1001/archopht.124.7.1046.
Longitudinal OCT texture analysis to assess the retinal changes in the triple‐transgenic mouse model of Alzheimer's disease
Authors: Bernardes Rui , Ghalati Maryam , Ferreira Hugo , Martins João , Guimarães Pedro , Moreira Paula , Ambrósio António , Castelo‐Branco Miguel , Serranho Pedro
Published: December 2022

Purpose: This study aimed to investigate whether texture from optical coherence tomography (OCT) can address Alzheimer's disease (AD)‐related changes in the retina by evaluating differences to the wild‐type (WT) control group over time.

Methods: The study included OCT data of WT mice and its age‐matched transgenic mice of AD (3xTg‐AD). Animals were imaged monthly from 1 month old up to 4 months old and at the ages of 8‐, 12‐, and 16 months old. Neuro‐retinal layers were analysed using various texture metrics, assuming that these could convey different views of unfolding changes. Two hundred forty texture metrics were computed from local binary patterns and some variants, local phase quantisation, wavelet features, and Gabor filters. The discriminative potential of the texture metrics was evaluated using the non‐parametric Mann–Whitney test with a 5% significance level at each age to determine the consistency in the texture difference between groups over time. The trajectories of the texture measurements of the WT and AD mice were compared to analyse the trends over time.

Results: Texture metrics showing differences between the WT and AD groups from a time‐point onwards were found for all neuro‐retinal layers, with the retinal nerve fibre layer (RNFL) presenting the most significant number of metrics in these conditions. The most relevant differences between groups were found at 2 months old, while few metrics presented differences from 8 months old onwards. Consequently, this study demonstrated that texture metrics discriminate retinas of AD mice from the WT group based on OCT data. Furthermore, this study also demonstrated the parallel path of changes over time in both groups, with the vast majority of the metrics presenting the same type of variation with time.

Conclusions: This study emphasizes the potential of the texture information in the OCT images to address AD‐related changes in the retina. We presented longitudinal texture analysis of WT and transgenic mice, where the texture differences were found at the youngest age of the study (1 month) and preserved the differences over the 16‐months study period. Those differences showed the same evolutionary trend for both groups.
Novel phenotype–genotype correlation with PEX6 gene in Saudi patients with Heimler syndrome
Authors: Almoallem Basamat
Published: December 2022

Purpose: Peroxisome biogenesis disorders (PBDs; MIM# 601539) are heterogeneous disorders caused by defects in genes encoding proteins that are essential for peroxisomal matrix and membrane proteins. Heimler syndrome is one of PBDs that is caused by mutations in PEX1 and PEX6 genes. In this study, we aimed to fully characterize the clinical and molecular aspects of two Saudi probands who were diagnosed early as Usher syndrome.

Methods: We set up a comprehensive clinical and molecular genetic workflow including detailed ophthalmological, audiological and systemic assessments followed by genome‐wide SNP microarrays analysis and targeted PEX6 gene screening by Sanger sequencing.

Results: Clinically: both patients appeared dysmorphic with long faces, high forehead, short nose, small low set ears, and full lips. The ophthalmological assessment revealed advanced inherited retinal dysfunction represented by waxy pallor optic disc, attenuated vessels, RPE mottling with intraretinal bony spicules pigmentations and central foveal atrophic changes in both eyes. Both Indexes exhibited bilateral sensory neural hearing loss and amelogenesis imperfecta. Genetically: an autozygous block was identified on chromosome 6p21.1 encompassing PEX6 gene using SNP microarrays. Novel PEX6 (NM_000287.3) c.290 T > G (p.Val97Gly) was found by Sanger sequencing. The identified variant co‐segregated with the phenotype in both families and found to be “likely pathogenic” according to ACMG guidelines.

Conclusions: Our study represents the first report of PEX6 associated Heimler syndrome in the middle east and considered to be the third in the literature so far. It highlights the importance of combining molecular diagnosis with the clinical findings to expand our knowledge of PEX6‐related PBDs phenotype and the allelic spectrum for this gene.
Corneal neovascularization associated with a novel PDGFRB gene variant: Implications for precision medicine treatment
Authors: Gladkauskas Titas , Bruland Ove , Safieh Leen , Deepak Edward , Rødahl Eyvind , Bredrup Cecilie
Published: December 2022

Purpose: To identify the genetic cause of aggressive corneal neovascularization arising in otherwise healthy children in one family. Further, to study molecular consequences associated with the identified variant and implications for possible precision medicine treatment.

Methods: Sanger sequencing of the candidate gene PDGFRB was performed in affected individuals. HeLa cells were transduced with wild type PDGFRB and the identified variant. Cells were treated with tyrosine kinase inhibitors (TKIs). ELISA and immunoblot analysis were used to detect phosphorylation of PDGFRβ and downstream signalling proteins.

Results: A novel variant in PDGFRB was found in affected family members. HeLa cells transduced with this variant did not have increased baseline levels of phosphorylated PDGFRb. However, upon stimulation with ligand, excessive activation of PDGFRb was observed in these cells compared to cells transduced with the wild type variant. Inhibition with some TKIs in vitro successfully prevented upregulation of PDGFRβ and its downstream signalling.

Conclusions: A novel substitution in PDGFRB was found in family members with isolated corneal neovascular overgrowth. Cells transduced with the variant showed increased phosphorylation upon ligand stimulation. While the examined TKIs had various effects in preventing such overactivation, this introduces the concept of precision medicine in preventing childhood blindness in these patients.
Tomographic prognostic factors for visual improvement after pars plana vitrectomy for epiretinal membrane
Authors: Nouri Slim , Amor Saloua Ben , Rekik Mouna , Ayedi Omar , Trigui Amira
Published: December 2022

Purpose: To evaluate postoperative changes and investigate tomographic prognostic factors of visual impairment after vitrectomy for epiretinal membrane (ERM).

Methods: A retrospective observational study on patients who underwent pars plana vitrectomy for ERM by a single experimented surgeon. Best corrected visual acuity (BCVA) on the logMAR chart and optical coherence tomography (OCT) features were recorded before surgery and at the last visit. Tomographic parameters analysed were: central foveal thickness (CFT), foveal contour morphology, external limiting membrane (ELM), ellipsoid zone (EZ) and interdigitation zone (IZ) integrity, the presence of intraretinal fluid (IRF), subretinal fluid, disorganization of retinal inner layers (DRIL) and subfoveal deposits. Student's t‐test and Pearson's correlation coefficients were used for statistical analysis. p Values <0.05 were considered statistically significant.

Results: Forty‐seven eyes of 43 patients were included. The mean age was 61.7 years (range 13–87). The ERM was idiopathic in 49% and secondary in 51%. The mean BCVA was 1.02 before and 0.5 after surgery and improved significantly (p < 0.001) with a mean gain of 5.2 lines. The postoperative BCVA correlated strongly with the preoperative one (R2 = 0,764, p < 0.001). Tomographic factors associated with worse final BCVA were higher baseline CFT (p = 0.004), abnormal foveal profile (p = 0.02), the presence of IRF (p < 0.001), DRIL (p = 0.01) and subfoveal deposits (p = 0.04). The disruption of ELM, EZ and IZ were as well associated with a poorer visual outcome (p < 0.001, p = 0.03 and p < 0.001 respectively).

Conclusions: ERM surgery provides functional and anatomical improvement. Preoperative OCT is an essential tool to evaluate morphological retinal changes and identify prognostic factors for visual recovery.
Keratitis fugax hereditaria ‐ useful to consider when you have a child with non‐specific corneal findings and symptoms
Authors: Immonen Annamari , Majander Anna , Kawan Sabita , Backlund Michael , Vasara Kristiina , Lindahl Päivi , Kivelä Tero , Turunen Joni
Published: December 2022

Purpose: To report clinical findings in children diagnosed with the autosomal dominant periodic corneal autoinflammation, keratitis fugax hereditaria (KFH, MIM 148200), and to highlight its geographical distribution.

Methods: Patients were clinically examined in the Helsinki University Hospital between February 4, 2006, and December 31, 2021, and genetically verified to be carriers of the c.61G > C (rs200154873) variant in NLRP3 by Sanger sequencing. Variant allele frequencies were determined from Genome Aggregation Database (gnomAD) version 2.1.1.

Results: The data consist of 10 children from 8 families; 6 boys and 4 girls. Age of onset varied from 3 to 14 (median, 8) years. Patients had typical KFH symptoms: eye pain, photophobia, conjunctival injection, and foreign body sensation. Five patients had corneal oval opacities, and 3 had a mild anterior chamber reaction. Seven were correctly diagnosed at the first visit based on family history. The remaining three children were diagnosed 1, 3, and 8 years after the first visit. Initial diagnoses were anterior uveitis, corneal erosion, and herpetic keratitis. Additionally, epithelial recurrent erosion dystrophy (ERED) or subepithelial mucinous corneal dystrophy (SMCD) had been suspected. Geographically, KFH concentrates to the bilingual Swedish‐speaking coastal areas of Finland. Allele frequencies are 0.014% in Finland, and 0.011% in Sweden, based on gnomAD.

Conclusions: Scandinavian ophthalmologists should be aware of the possibility of KFH in case of suspected anterior uveitis, herpetic keratitis, or recurrent corneal erosion in children. Symptoms of paediatric KFH patients are equal to those in adults, but the typical corneal opacity still might recover between the attacks.
Evaluation of the neuroprotective effect of metformin in diabetic patients with glaucoma
Authors: Martucci Alessio , Carlucci Federico , Satriano Andrea , Cesareo Massimo , Russo Rossella , Nucci Carlo
Published: December 2022

Purpose: Metformin, a biguanide used to treat diabetes, reduced neuroinflammation in vitro and in vivo and resulted neuroprotective in experimental Parkinson's disease. Metformin has also recently been shown to promote neurogenesis (1). The study aims to evaluate the putative neuroprotective effect of metformin in glaucomatous diabetic patients.

Methods: For this retrospective pilot study, clinical notes of glaucomatous diabetic patients of the ophthalmological department of the University Hospital of Rome Tor Vergata were reviewed. Among all, 15 patients were compliant with the inclusion criteria. Patients were then divided into 2 sub‐groups: the Glaucoma group treated with metformin (n = 16 eyes) and the Glaucoma group treated with insulin (n = 14 eyes). Any glaucoma treatment was accepted with exception of brimonidine, citicoline, and coenzyme Q10. Patients must have performed in their clinical history two 24‐2 visual field examinations carried out 6 months apart.

Results: Patients were homogeneous in terms of age (p = 0.09) and gender (p > 0.73). Metformin and Insulin groups were homogeneous in terms of Mean Deviation (MD) and Pattern Standard Deviation (PSD) at baseline (T0) (p = 0.70 and p = 0.73 respectively). After 6 months (T1) MD did not change significantly in the metformin group (p = 0.64). On the contrary, at T1 MD significantly worsened in the Insulin group (p = 0.01). No difference was found in terms of PSD in both groups. The visual field Index did not change in the Metformin group while significantly worsened in the Insulin group (p = 0.03).

Conclusions: This study suggests for the first time a possible neuroprotective effect of metformin in glaucomatous diabetic patients. Patients under Metformin did not show a worsening of the visual field test in 6 months. Conversely, patients under Insulin worsened. Other prospective are required to confirm our results.

Reference

1. Rotermund C, Machetanz G, Fitzgerald JC. The Therapeutic Potential of Metformin in Neurodegenerative Diseases. Front Endocrinol (Lausanne). 2018; 9: 400. doi: 10.3389/fendo.2018.00400. PMID: 30072954; PMCID: PMC6060268.
Glaucoma and cardioprotective medication
Authors: Horwitz Anna , Klemp Marc , Andreasen Jens , Horwitz Henrik , Freiberg Josefine , Torp‐Pedersen Christian , Kolko Miriam
Published: December 2022

Purpose: To investigate the impact of cholesterol‐lowering medication, anticoagulants, and antihypertensive medication on the onset of glaucoma in Denmark from 1996 to 2018.

Methods: We included all 2.5 million Danish individuals over 40 years of age. We used the National Danish Registry of Medicinal Products Statistics to identify all claimed prescriptions for glaucoma medication, cholesterol‐lowering medication, anticoagulants and antihypertensives. Glaucoma was defined as having three claimed prescriptions, being diagnosed in hospital or having undergone glaucoma surgery.

Results: We first employed a cross‐sectional study design. We found that patients treated with cardioprotective medication have a significantly higher overall risk rate for glaucoma than those who do not take the medication after controlling for a range of factors. In particular, we found that cholesterol‐lowering medication (RR of 1.46, p < 0.0001), anticoagulants (RR of 1.36, p < 0.0001) and antihypertensive medication (RR of 1.35, p < 0.0001) all were significantly correlated with an increased risk of glaucoma. Furthermore, all three medications remain significantly correlated in a joint analysis, with the strongest association seen between glaucoma and cholesterol‐lowering medication. We then employed a panel data study design. We found that cholesterol‐lowering medication, anticoagulants, and antihypertensive medication are each significantly positively associated with glaucoma within 2‐ and 5‐year intervals. Finally, we employed a regression discontinuity study design. We confirmed a previous finding showing that antihypertensive medication has an apparent causal negative effect on the risk of developing glaucoma. Moreover, we found that prescription of cholesterol‐lowering and anti‐glaucomatous medication have similar causal effects.

Conclusions: Overall, the present study indicates that cardioprotective medication may have a preventive effect on the development of glaucoma.
Therapeutic approach in non‐proliferative diabetic retinopathy using antioxidant supplementation
Authors: Campos‐Borges Helena Cristina , Pinazo‐Duran Maria Dolores , Andres‐Blasco Irene , Garcia‐Medina Jose Javier , Zanon‐Moreno Vicente , Gallego‐Martinez Alex , Salgado‐Borges Jose Manuel , Duarte Lilianne , Prudêncio Cristina
Published: December 2022

Purpose: Overproduction of reactive oxygen species (ROS) leads to eye damage and causes effects of ROS signalling pathways. In this work, we evaluated oxidative stress (OS) biomarkers and the effects of a daily supplementation regimen containing antioxidants and essential fatty acids (A/ω3) in type 2 diabetic eyes (T2DM).

Methods: This is a case–control study involving 480 participants, divided into 2 groups: (1) T2DM patients (n = 287) with (+)/without (−) non‐proliferative diabetic retinopathy (NPDR) and (2) controls (CG; n = 194)). Participants were randomly assigned to a daily pill of A/ω3. Patients were followed‐up for 38 months, allowing to outline patient characteristics, NPDR status, and classical and emerging blood parameters, including OS markers (candidate products and genes). Statistical analysis was performed using the SPSS 24.0 program.

Results: Significantly higher levels of circulating pro‐oxidants (p = 0.001) and lower levels of antioxidants (p = 0.0001) were detected in patients with T2DM versus CG. Plasma malondialdehyde/thiobarbituric acid reactive species were significantly higher (MDA/TBARS; p = 0.006) and lower antioxidant load, based on the total antioxidant capacity of plasma (TAC; p = 0.042) and vitamins B12 (p = 0.05) and C (p = 020) levels were found inT2DM + NPDR versus T2DM‐NPDR. Overexpression of the matrix metalloproteinase‐9 (MMP‐9) gene was found in T2DM + NPDR versus T2DM‐NPDR and in GC (p = 0.021). It is important to note that the therapeutic regime with A/ω3 supplementation in all groups proved to be beneficial, particularly in the group of patients with diabetic retinopathy (DR).

Conclusions: This study stresses the need for new strategies to increase the antioxidant load, as in the case of the A/ω3 supplementation regime, which can serve as a dietary prophylaxis and adjunctive intervention for better ophthalmic care in patients at risk of associated blindness to DR.
Evaluation of the effect of cigarette smoking on retina and choroid: An optical coherence tomography angiography study
Authors: Sassi Hela , Aoun Safa Ben , Fekih Khawla , Nouri Slim , Mzoughi Khadija , Cheour Monia
Published: December 2022

Purpose: To study the effect of active cigarette smoking on retinal and choroidal micro‐vascularization using Swept Source Optical Coherence Tomography Angiography (SS‐OCT A).

Methods: This is a cross‐sectional, observational, comparative study carried out at the Ophthalmology department of Habib Thameur University Hospital of Tunis. Twelve eyes of “healthy” smokers, 10 eyes of former smokers (less than 3 years after quitting smoking) and 6 eyes of healthy non‐smokers controls were included. SS‐OCT A 3 × 3 mm angiograms were exported and analysed with image J, Fiji Software. Perimeter of avascular central zone (ACZ), superficial retinal plexus density (SRPD), deep retinal plexus density (DRPC) and choriocapillaris capillary vessel density (CVD) were calculated and analysed. Comparative Kruskal Wallis and Spearman tests were performed using 21.0 SPSS.

Results: Volunteers with a smoking history had an average of 13.75 ± 10.26 pack‐years. The mean smoking period was 3.2 ± 5.13 years and mean smoking cessation period was 1.28 ± 0.85 years. Mean ACZ, SRPD, DRPD and CVD were respectively 2.62 ± 0.52 mm, 13.20 ± 2.10%, 17.14 ± 1.17% and 51.05 ± 0.85%. There was no significant difference between the three groups for the measurements of ACZ, SRPD, DRPD and CVD (p = 0.57, p = 0.97, p = 0.53 and p = 0.07; respectively). However, there was a significant positive correlation between the smoking cessation period and the DRPD (p = 0.003, r = 0.865).

Conclusions: Despite the known effects of nicotine and other chemical substances in cigarettes on peripheral vascular structures, no significant difference in quantitative analysis of retinal and choroidal networks could be found. Deep retinal plexus density seems to increase after long smoking cessation periods.
Pigment epithelium and choroid changes in pachychoroid pigment epitheliopathy: A descriptive study
Authors: Abid Yosra , Sassi Hela , Chaabouni Karim , Ouederni Meriem , Maamouri Rim , Cheour Monia
Published: December 2022

Purpose: To describe characteristic elementary lesions of retinal pigment epithelium and choroidal vascular parameters determined by swept source optical coherence tomography (SS‐OCT) and OCT‐angiography (OCT‐A) in eyes with pachychoroid pigment epitheliopathy.

Methods: Twenty‐seven patients with retinal pigment epithelium (RPE) abnormalities associated to pachychoroid features, with no history or findings indicative of subretinal fluid or soft drusen were evaluated. All eyes underwent comprehensive ophthalmic examination, fundus photography, SS‐OCT and OCT‐A. After binarization of B‐scan images with ImageJ Software, the choroidal vascularity index (CVI), the choroidal vascularity proportion (CVP) and flow voids area were calculated.

Results: A total of 27 eyes of 23 patients, 19 of whom were male (70.37%), with a mean age of 59.11 ± 12.76 years were enrolled in this study. We detected six different types of RPE lesions: focal disruption in ellipsoid and interdigitation zones in 18 eyes (66.66%), RPE elevation with microbreak appearance in 12 eyes (44.44%), RPE thickening in 10 eyes (37.03%), small pigment epithelium detachment in seven eyes (25.92%), RPE spike in five eyes (18.51%) and outer nuclear layer thinning in five eyes (18.51%). The subfoveal choroidal thickness (SFCT) was 399, 78 ± 88, 13 μm. The mean inner choroidal thickness was 87.18 ± 36.67 μm. The CVI was 65.28 ± 3.35%. The CVP was 59.10 ± 0.58% in the choriocapillaris and 59.69 ± 1.42% in the Haller layer. The total choriocapillaris flow void area was 39.87 ± 1.21%.

Conclusions: SS‐OCT and OCT‐A are valuable diagnostic tools to characterize pigment epithelium and choroidal changes in PPE eyes.
Synchrotron‐based FTIR microspectroscopy of human primary retinal pigmented epithelial cells as a model for age‐related macular degeneration
Authors: Josifovska Natasha , Andjelic Sofija , Lumi Xhevat , Ducic Tanja , Petrovski Goran
Published: December 2022

Purpose: To investigate the characteristics of untreated and treated human retinal pigmented epithelial cells (hRPEs) as an ex vivo model for age‐related macular degeneration (AMD) using high resolution synchrotron radiation‐based Fourier Transform Infrared (FTIR) microspectroscopy and multivariate analysis.

Methods: hRPEs obtained from cadavers were treated by autophagy ‐inducer rapamycin (Rap), and ‐inhibitor bafilomycin A1 (Baf), as well as hydrogen peroxide (H2O2) to induce oxidative stress, in an ex vivo model for studying AMD. FTIR measurements were performed at the MIRAS beamline of the ALBA Synchrotron, Barcelona, Spain.

Results: The FTIR spectra consisted of several bands arising from the vibration of different groups belonging to proteins, lipids and nucleic acids, indicating the rich biochemical composition of the hRPEs. In the protein region, the amide I band of the treated groups (Rap, Baf, H2O2) was different from the control untreated group, indicating an overall protein disordering under such treatments. In the DNA region, two spectral areas appeared to be modified upon treatment, indicating different modifications of the DNA conformational changes or rearrangements attributed to the distortions of the DNA double helix in the presence of Rap, Baf or H2O2. The same treatments could also induce several modifications in the lipid spectral region, which can affect a wide range of biological processes. The H2O2 treated group showed higher prevalence for the lipid peroxidation, a process generated by the effect of several reactive oxygen species.

Conclusions: The present study shows that high resolution FTIR can be used to evaluate the complete bio−/macro‐molecular spectra of hRPEs such as proteins, lipids and nucleic acids, which can be used as an ex vivo model for AMD, thus giving possibilities for developing and testing new treatment modalities.
The phase 3 REFLECT trial: Efficacy and safety of bilateral gene therapy for Leber hereditary optic neuropathy (LHON)
Authors: Yu‐Wai‐Man Patrick , Newman Nancy , Subramanian Prem , Moster Mark , Wang An‐Guor , Donahue Sean , Leroy Bart , Carelli Valerio , Biousse Valérie , Vignal‐Clermont Catherine , Sadun Alfredo , Sergott Robert , Fernández Gema Rebolleda , Chwalisz Bart , Banik Rudrani , Cox Eric , Roux Michel , Taiel Magali , Sahel José‐Alain
Published: December 2022

Purpose: To evaluate the efficacy and safety of a bilateral injection of lenadogene nolparvovec in patients with Leber Hereditary Optic Neuropathy (LHON) carrying the m.11778G > A mutation.

Methods: REFLECT is a randomized, placebo‐controlled, phase 3 study that included 98 patients with vision loss ≤1 year at enrolment. Patients received a single intravitreal injection of lenadogene nolparvovec (9E10 viral genomes per eye) in their first‐affected eye. The second‐affected eye was randomized to a second injection of gene therapy or placebo.

Results: A total of 48 patients were treated bilaterally and 50 unilaterally. At 1.5 years, the change from baseline in best‐corrected visual acuity (BCVA) of the second‐affected eyes was not statistically different between the two arms (primary endpoint). Two years after injection, a statistically significant improvement in BCVA was reported from baseline in treated eyes. Mean BCVA showed an absolute difference between the arms of +6 ETDRS letters in favour of bilaterally treated patients. The improvement from nadir was +20 and +17 letters for the first‐ and second‐affected eyes treated bilaterally, and +19 and +14 letters for first‐ and second‐affected eyes treated unilaterally (all p < 0.0001). Clinically meaningful improvement from nadir ≥ +15 letters was found in the majority of bilaterally and unilaterally treated patients (73% and 66%, respectively). The main ocular adverse event related to gene therapy was intraocular inflammation, which was mostly mild and responsive to conventional treatment. Overall, the safety profile was favourable and comparable in patients treated unilaterally and bilaterally.

Conclusions: The 2‐year data confirm the results observed 1.5 years after treatment: bilaterally treated patients have better improvement of BCVA than unilaterally treated patients with a favourable safety profile. Placebo eyes showed a contralateral therapeutic effect as previously observed in the RESCUE and REVERSE trials.
ocular surface health affects the quality of life of the elderly
Authors: Aapola Ulla , Nättinen Janika , Tuomilehto Jaakko , Keinänen‐Kiukaanniemi Sirkka , Saramies Jouko , Uusitalo Hannu
Published: December 2022

Purpose: To examine the association of ocular surface health with the quality of life (QoL) in a population‐based cohort of older people.

Methods: This cross‐sectional study included 601 subjects born between years 1933–1956 and living in Savitaipale, Finland. Various ocular surface health parameters were evaluated, including Schirmer's I test, non‐invasive tear break‐up time (NIBUT), corneal and conjunctival staining, conjunctival redness, blepharitis, Meibomian gland dysfunction (MGD), and Ocular Surface Disease Index (OSDI). For QoL measurements 15D, Medical Outcomes Study 36‐Item Short Form Health Survey (MOS SF‐36), and Beck's Depression Inventory.

(BDI‐II) were used. Multiple linear regression was used to examine the effects of ocular surface health on QoL.

Results: OSDI scores affected majority of the MOS SF‐36 scales as well as 15D and BDI‐II scores (p < 0.05). BDI score worsened with increasing corneal and conjunctival staining and MGD scores (p = 0.004, p = 0.001, and p = 0.03, respectively). Physical and emotional health‐associated role limitations increased with increased conjunctival redness (p = 0.007 and p = 0.005, respectively). In addition, emotional well‐being was affected by conjunctival redness, blepharitis, MGD, and NIBUT (p < 0.05).

Conclusions: The symptoms experienced by the participants affect various aspects of well‐being according to our results. Of the ocular surface signs, the ocular surface tissue defects appear to play more significant role in worsening of the general health‐related QoL, whereas the aqueous deficiencies alone do not. The health of ocular surface is an important factor of the QoL and merits to be taken account in clinical assessment of people and these symptoms should be treated accordingly.
New onset of acute uveitis following COVID‐19 vaccination
Authors: Sim Haeun , Jeong Jeonga , Kang Min Ji , Hwang Jehyung
Published: December 2022

Purpose: This study reported 11 cases of new‐onset acute uveitis following coronavirus disease 2019 (COVID‐19) vaccination.

Methods: This retrospective observational case study included 11 eyes from 11 patients with acute uveitis after COVID‐19 vaccination. We only included patients with new‐onset uveitis. Patients' medical records from January 2021 to January 2022 were reviewed.

Results: The mean age of the participants was 51.81 years, and all patients demonstrated anterior chamber reaction with keratic precipitates in the affected eye. The mean duration between vaccination and uveitis was 8.27 days. Seven patients developed uveitis after receiving the second vaccination, and four developed uveitis after receiving the third vaccination. Five patients showed posterior synechiae and three patients showed hypopyon. After treatment with topical 1% prednisolone acetate eye drops and systemic prednisolone, inflammation was adequately controlled and quickly resolved.

Conclusions: COVID‐19 vaccination with messenger RNA and viral vector vaccines may cause acute anterior uveitis. Although initially severe, the patients' uveitis responded well to steroid therapy, without visual impairment.

References

1. Aslam S, Goldstein DR, Vos R, et al. COVID‐19 vaccination in our transplant recipients: The time is now. J Heart Lung Transplant 2021; 40:169–171.

2. Calina AO, Docea D, Petrakis D, et al. Towards effective COVID19 vaccines: updates, perspectives and challenges (review). Int J Mol Med 2020; 46: 3–16.

3. Ramasamy MN, Minassian AM, Ewer KJ, et al. Safety and immunogenicity of ChAdOx1 nCoV‐19 vaccine administered in a prime‐boost regimen in young and old adults (COV002): a single‐blind, randomized, controlled, phase 2/3 trial. Lancet 2021, 396: 1979–93.
Association between parapapillary choroidal microvasculature and prognosis of optic neuritis
Authors: Bae Hyoung Won , Lee Jihei , Kim Chan Yun
Published: December 2022

Purpose: To identify peripapillary choroidal MvD in eyes with optic neuritis and its association with longitudinal changes in retinal nerve fibre layer (RNFL) and ganglion cell‐inner plexiform layer (GCIPL) thicknesses following diagnosis.

Methods: A total of 48 eyes with optic neuritis was evaluated to identify the presence of peripapillary choroidal MvD, defined as a focal capillary loss with no visible microvascular network in choroidal layer, using optical coherence tomography (OCT) angiography (OCTA). Patients were divided based on the presence of MvD. OCT and standard automated perimetry (SAP) conducted at 1, 3 and 6 months follow‐up were analysed.

Results: MvD was identified in 20 of 48 eyes (41.7%) with optic neuritis. MvD was most commonly found in the temporal quadrant (85.0%), and peripapillary retinal vessel density in the temporal quadrant was significantly lower in eyes with MvD (p = 0.012). At 6 months follow up, optic neuritis eyes with MvD showed significantly thinner RNFL in the temporal quadrant (p = 0.012) and GCIPL in all sectors (p = 0.007). No significant difference was noted in SAP parameters. The presence of MvD was significantly associated with thinner global GCIPL thickness at 6 months follow‐up (OR 0.905, 95% CI 0.832–0.984, p = 0.019).

Conclusions: Optic neuritis showed peripapillary choroidal microvascular impairment in the form of MvD. MvD was associated with structural deterioration at macular GCIPL. Further studies are necessary to identify the causal relationship between microvascular impairment and retinal nerve fibre layer damage in optic neuritis.
How ready is artificial intelligence (AI) for clinical use?
Authors: Zakri Rosina , Davies Nigel
Published: December 2022

Purpose: Use of Artificial Intelligence (AI) as a diagnostic tool or clinical decision support tool has been investigated extensively. The purpose of this study is to review the literature to date, the number and type of systems that are already available.

Methods: A search of MEDLINE, Embase, Cochrane Review, and Global Health Library (2000–2022) was performed. Key words used were Ophthalmology AND AI OR Clinical Assist OR Decision Support Tools. Inclusion criteria were articles written in the English language and studies with human participants. Exclusion criteria were editorials, articles using animal models, and pure validation studies.

Results: 11 557 papers when ‘Ophthalmology and AI’ filtered applied, and 906 when ‘Decision Support Tool’ is specified. 387 titles filtered for inclusion/exclusion criteria, of which 26 working tools were identified, (Cataract 4, Cornea and refraction 3, Melanoma 2, Oculoplastic 3, Paediatric Ophthalmology 1, Triage 2, Glaucoma and Neuro‐Ophthalmology 4, Retina 7). Of these, 6 are available for clinical use.

Conclusions: Out of a large number of studies, we find 6 examples of Diagnostic or Decision support tools ready for implementation. Two are diagnostic, based on input of risk factors alone, and the others use image analysis for disease management and screening. Most AI work is retrospective and observational in nature, with most trials in medical retinal diseases. Further work is needed to translate AI ideas into clinical practice.
Assessment of the impact of an early acute immune challenge on the diabetic retina
Authors: Fernandes Hugo , Cruz Alexandra , Boia Raquel , Gaspar Rita , Nunes Sara , Baptista Filipa , Ambrósio António Francisco
Published: December 2022

Purpose: Diabetic retinopathy (DR) is a leading cause of blindness worldwide. It has been claimed that infections may enhance the progression of retinal degenerative diseases to more severe stages. Infections prime microglia, the immune cells of central nervous system. Microglia‐mediated neuroinflammation is a hallmark of DR. We hypothesized that an infection at adolescence negatively impacts on the retina later in life when it is challenged with diabetes.

Methods: An infection was mimicked by an intraperitoneal injection of lipopolysaccharide (LPS), in Wistar rats. Diabetes was induced by streptozotocin. Retinal function was assessed by electroretinography and retinal structure was evaluated by optical coherence tomography (OCT). Microglia reactivity was assessed by immunolabelling Iba‐1 and MHC‐II.

Results: We evaluated first the impact of LPS per se on the retina. Scotopic threshold response, indicative of retinal ganglion cell function, presented a significant decreased amplitude 30 days after LPS injection, without alterations in the function of other retinal neurons. OCT revealed that 1 day after LPS there was an increase in the thickness of inner retinal layers. Eye fundus images showed a thickening of retinal vessels and the presence of vitreous infiltrates, 1 and 5 days after LPS injection. LPS also significantly increased microglial reactivity 1 day after the injection. Then, we evaluated the impact of LPS when the retina was also exposed to a diabetic insult (30 days). In diabetic animals previously exposed to LPS, there was a decrease in the amplitude of cone response, evaluated by flicker (first and second harmonic).

Conclusions: LPS per se affects the retina in several parameters, mainly in the first days upon LPS challenge. Moreover, LPS priming negatively impacts on cone cell function upon diabetes.

Supported by FCT, Portugal (PEst UIDB/04539/2020 and UIDP/04539/2020) and Centro 2020 Regional Operational Programme (CENTRO‐01‐0145‐FEDER‐000008: BrainHealth 2020).
Application of Thealoz® duo eye drops confers novel protective effects on the ocular surface of dry eye patients
Authors: Perumal Natarajan , Jeong Eunjin , Runde Sarah , Manicam Caroline , Pfeiffer Norbert , Grus Franz
Published: December 2022

Purpose: The protective effect of Thealoz® Duo eye drops was investigated in patients with dry eye syndrome (DES) by clinical examination. Subsequently, the tear proteome alterations were characterized employing the mass spectrometry‐based proteomics platform.

Methods: Fifty‐eight subjects underwent thorough clinical investigation for DES, namely the ocular surface disease index (OSDI), and were grouped as mixed DES (DRY, N = 35) and healthy (CTRL, N = 23). A DRY subgroup of severe aqueous‐deficient DES (sDRYaq, N = 12) was also clinically identified. Only DES patients were subjected to application of Thealoz® Duo (trehalose 3% and hyaluronic acid 0.15%). All subjects were scheduled for clinical investigation before (day 0, T0) and after day 28 ± 4 (T28) and 56 ± 4 (T56) of Thealoz® Duo application. Next, 174 individual tear samples from both groups at two time‐points were subjected to in‐depth proteomics and bioinformatics analyses.

Results: Application of Thealoz® Duo (4.2 ± 0.9 times/day) significantly improved the OSDI in DRY at T28 vs. T0 (p = 4.1 E‐3) and T56 vs. T0 (p = 2.0 E‐5). Proteomics analysis resulted in the identification of 128 and 291 significantly (p < 0.05) differently abundant proteins in DRY vs. CTRL and sDRYaq vs. CTRL, respectively. Interestingly, Thealoz® Duo application after only T28 resulted in significant activation of various molecular processes, mainly the antibacterial response (DRY vs. CTRL, p = 2.3 E‐4; sDRYaq vs. CTRL, p = 5.7 E‐5), metabolic pathways (DRY vs. CTRL, p = 4.9 E‐3; sDRYaq vs. CTRL, p = 4.7 E‐6) and inhibition of apoptosis (DRY vs. CTRL, p = 4.1 E‐4; sDRYaq vs. CTRL, p = 8.9 E‐17). Importantly, the activated inflammatory process at T0 in DRY (p = 9.7 E‐4) and sDRYaq (p = 2.0 E‐8) were significantly inhibited at T56 following the continuous use of Thealoz® Duo.

Conclusions: For the first time, this comprehensive investigation unravelled novel mechanistic processes attributed to the efficacy of Thealoz® Duo eye drops, which significantly improved vision‐related functions in mixed and severe DES patients.