bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum microRNAs as biomarkers associated with the course of diabetic macular oedema
Authors: Aragona Emanuela , Arrigo Alessandro , Aguennouz M' Hammed , Aragona Pasquale , Bandello Francesco
Published: January 2024

Aims/Purpose: Intravitreal drugs are powerful therapies for diabetic macular edema (DME), but the clinical course and the response to treatments still remains unpredictable. MicroRNAs (miRNAs) represent a class of small molecules associated with the regulation of several metabolic pathways, including diabetes. However, their use in the clinical setting of DME is limited by lack of data regarding the correlation with clinical and imaging features. In the present study we evaluated some miRNAs profiles obtained by serum samples of newly diagnosed DME patients.

Methods: Prospective study, including baseline visit (V0), a 4‐months visit (V1) and a 12‐months visit (V2). At V0 patient underwent serum sampling, imaging was repeated at every study visit. Enriched serum microRNAs were extracted and real‐time PCR was performed. OCT features were used to assess the severity and progression of the disease.

Results: We collected data of a cohort of type 1 and type 2 diabetic patients. All the patients presented DME and were naïve to intravitreal treatments. The follow‐up was of 12 months. Diabetes‐related miRNAs were found up‐ or downregulated and associated with the course of DME (resolved/recurrent/persistent). Correlations were found with imaging biomarkers.

Conclusions: On the basis of these findings, serum miRNAs assessment is a feasible and clinically relevant assessment to be performed in the diagnostic work‐up of diabetic patients affected by DME. MiRNAs might pave the basis for customized treatment strategies to optimize the management of DME.

References

1. Mastropasqua R, Toto L, Cipollone F et al. Role of microRNAs in the modulation of diabetic retinopathy. Prog Retin Eye Res. 2014.

2. Arrigo A, Aragona E, Capone L et al. Foveal Eversion: A Possible Biomarker of Persistent Diabetic Macular Edema. Ophthalmol Ther 2021.

3. Arrigo A, Capone L, Lattanzio R et al. Optical Coherence Tomography Biomarkers of Inflammation in Diabetic Macular Edema Treated by Fluocinolone Acetonide Intravitreal Drug‐Delivery System Implant. Ophthalmol Ther 2020.

4. Arrigo A, Aragona E, Battaglia Parodi M, Bandello F. Quantitative approaches in multimodal fundus imaging: State of the art and future perspectives. Prog Retin Eye Res. 2023.
Leber hereditary optic neuropathy. The Dutch approach
Authors: Lushchyk Tanya , van Everdingen Judith
Published: January 2024

Aims/Purpose: To share the structure of care for patients with Leber Hereditary Optic neuropathy (LHON) in the Netherlands. This includes the role of Expertise centers in coordinating rapid diagnosis and start of treatment, as well at the introduction of a specific database to track data of patients with LHON.

Methods: Dutch LHON Expertise centres are organized to act as central points for patient referrals from regional hospitals with the aim to speed up the diagnostics and treatment of LHON patients. The database of Dutch LHON patients has been created and is online today, to provide demographical, epidemiological, clinical characteristics and effects of treatment with Idebenone on disease progression.

Results: Three LHON Expertise centers provide fast diagnostic, coaching and treatment services in the whole of the Netherlands. Patient referral is done easily due to the small geography. A DNA test on primary and non‐primary mtDNA mutations is performed as standard, including the DNAJC30 gen. Additional parameters are obtained to monitor disease progression: Visual Acuity Score by ETDRS letters chart, HRR colour tests, OCT of ganglion cell layer and retinal neurofibral layer, Visual field by Goldmann kinetic perimetry or Humphry static perimetry. All patients have access to a social worker. They are provided with a flyer about LHON disease and contact details of the relevant patient association.

Conclusion: A thoroughly organized clinical path for LHON patients provides rapid diagnostics and start of treatment. Patients referrals is done easily and treatment delay minimized. The centralization of Dutch LHON patients in three expertise centres enables us to maintain a central database with important clinical and epidemiological data. This information is relevant to optimize current therapy options with Idebenone and also for supporting future studies on novel therapy options.
Diagnosis of non‐strabismic binocular vision anomalies ‐ why are there so many different approaches?
Authors: Evans Bruce
Published: January 2024

Aims/Purpose: To review and contrast the main approaches for diagnosing and managing non‐strabismic binocular vision anomalies (BVA), including decompensated heterophoria, binocular instability, accommodative anomalies.

Methods: A literature search was undertaken to determine the main methods of diagnosing and correcting/treating BVA. Findings from leading textbooks were compared with research literature. The literature was filtered by country and by profession to investigate factors that may contribute to diversity of approaches.

Results: The literature searches reveal marked variation in the methods recommended for diagnosing BVA. There is agreement concerning the interventions available (refractive correction, prisms, eye exercises, surgery). However, there are diverse opinions concerning the criteria for determining when treatment is required. For refractive correction or prisms, the evidence suggests that different methods used for determining the correction required will lead to different prescriptions. To some extent, the variation can be attributable to national differences. However, even within some countries, very diverse diagnostic criteria and prescribing philosophies are evident. A wide variation sometimes is present within as well as between the different eyecare professions.

Conclusions: Research with standardized patients indicates, clinical practice is likely to be even more varied than the review indicates. The wide variation means that even within a country/profession, a patient may consult two practitioners and receive different diagnoses, or dissimilar interventions. One reason for the variation is likely to be the historical influence of prominent clinicians/teachers. Evidence‐based scrutiny should be applied to old methods as well as new. Research is required that compares different philosophies for diagnosis and prescribing.
School eye screening survey in the Gaza Strip/Palestine
Authors: Mikki Nahed
Published: January 2024

Aim: To estimate prevalence of vision impairment and associated refractive error in basic school children in the Gaza Strip in the State of Palestine. The study will also provide an estimate of the use of corrective spectacles among children with refractive error. Associated factors like age, sex, type of school, residence, parents’ education, parents’ occupation, other indicators of socio‐economic status and vision problems in the child and the family will be studied.

Methods: This is the first comprehensive study of school children vision impairment in the Gaza Strip.

The method is an adaptation of WHO's Assessment of the prevalence of visual impairment attributable to refractive error or other causes in school children (RESC) methodology.

Study population are students in the first and the nineth grades from public and United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) schools in the Gaza Strip.

The sampling unit (cluster) was classes in the target grade levels and the strata were grade (grade 1 and grade 9), type of school (public and UNRWA) and school gender (all male, all female and co‐ed schools).

Based on an expected prevalence of blindness of 20% among target population, 95% confidence level, 20% non‐response rate (refusals and absent students/total number of students), 3.4% margin of error and a design effect of 1.35 to account for clustering, a sample size 1100 students was determined. 28 classes were selected with probability proportionate to size from a list of classes of target grades along with number of children enrolled within each class in public and UNRWA schools in the Gaza Strip.

Results: The actual number of students was 1094 in 15 UNRWA and 13 public schools (15 first grade classes and 13 ninth grade classes). The total non‐response rate was 12%.

Data collection was completed on 18.5.2023. I did not have time to clean and analyse the data. Results will be presented at the conference.

Conclusions: Conclusions will be presented at the conference.
The predictive value of parameters of optic disk in evaluating the progression of myopia
Authors: Huseva Yuliya , Zharikova Olga
Published: January 2024

Aims/Purpose: To analyse the parameters of the optic nerve head (ONH) as markers of the progression of myopia with the usage of optical coherence tomography (OCT).

Methods: 72 patients (144 eyes) aged 9–57 years with myopia were investigated. The standard OCT parameters of the ONH, the ovality index (OI), the zone of parapapillary atrophy (PPA), location of the lamina cribrosa (LC) of the sclera and the trunk of the central retinal vessels (CRV) were evaluated. Data was statistically approved.

Results: A positive correlation between the axial length (AL) and the optic disc cup area, its horizontal and vertical diameters was found. Whilst the volume and the depth of the optic disc cup increased till the AL reached a certain critical value (26.3 mm) with subsequent reduction. An inverse correlation between the AL and the neuroretinal rim area, volume and rim/disc ratio was revealed. These changes in the ONH can be explained by scleral remodelling during elongation of the eye. Formation of γ‐zone PPA and an increase in the β‐zone PPA was accompanied by the tendency of thinning of the retinal nerve fibre layer (RNFL) in the inferior, nasal‐superior and superior sectors of the ONH. In 27.63% cases tilted optic discs were noted, of which 61.90% were vertically and 38.1% ‐ horizontally tilted. The direction of the tilt was determined by the location of the PPA zone with a tendency to thinning of the RNFL in the same sectors. A positive correlation between the AL of eye and the location of the LC of sclera was found. In 29.17% the superficial location of the LC was determined. In 54.17% elongation was accompanied by displacement of the trunk of the CRV on ONH in the nasal ‐ 71.79%, or in the superior‐nasal direction ‐ 28.21%.

Conclusions: The revealed changes of optic disc cup, neuroretinal rim and the parapapillary zones; a superficial displacement of LC of sclera and ‘nasalization’ of the trunk of CRV; a decrease in the OI with growth in the AL; relationships of the PPA zone with a tendency to thinning of the RNFL and direction of the tilt can be useful as OCT markers in interpreting normative data in patients with myopia, predicting its progression, and also in differential diagnosis with glaucomatous optic neuropathy.
Current status & outcomes of the Welsh national cohort of patients with leber's hereditary optic neuropathy treated with idebenone
Authors: Sanders Francis W. B. , Votruba Marcela
Published: January 2024

Aims/Purpose: To assess the real‐world effectiveness of idebenone in a heterogenous group of patients with LHON treated with idebenone in Wales. This provides insight into the national outcomes of.

Methods: Patients were identified from the ophthalmic genetics service based at Cardiff Eye Unit. Clinical notes were reviewed and details were collated on: demographics of patients, genetic mutation ascribed to be causative of LHON, visual acuity from diagnosis through to March 2023. Visual acuity was analysed for clinically relevant recovery (CRR) defined as improvement from “off‐chart” to at least 5 letters “on‐chart” or “on‐chart” improvement of at least 10 letters.

Results: 11 patients with LHON were identified as being treated with Idebenone 300 mg TDS. Currently 45.9 ± 20.3 years of age (range 22–73). 8 male and 3 female patients. 6 patients had the m11778G > A mutation and 4 patients had the m14484T>C. Disease duration at treatment onset ranged from 2 to 216 months with a mean of 35.8 months. Patients had a mean duration of treatment of 14 months (range 6–20). 2 eyes in one patient demonstrated CRR improving from a nadir of 6/60 and counting fingers acuity to 6/6 and 6/7.5 respectively. All other patients demonstrated no CRR at the time of data collection.

Conclusions: Idebenone has mixed results in a heterogenous group of patients with LHON providing significant benefit for one patient out of a cohort of 12, meanwhile others demonstrated limited improvements, albeit prior to a full two‐year course of treatment. It remains to be seen what the long‐term outcomes will be with sustained treatment with idebenone.
Presentations patterns of acute onset binocular diplopia among paediatric population in the emergency department: Retrospective analysis and systematic review of the literature
Authors: Fustel Paula Boned , García Laura Fernández , Martí M. Ángeles Ruth Bort , González Honorio Barranco
Published: January 2024

Aims/Purpose: This study aims to analyse the available evidence to identify the presentation patterns and underlying etiologies among paediatric patients presenting with acute onset binocular diplopia (AOBD) in the emergency department (ED).

Methods: A longitudinal retrospective analysis of medical records from paediatric patients, younger than 21 years old, presenting with AOBD in a tertiary hospital's ED. All patients were followed until a final diagnosis was made. Emergent conditions (ECs) were defined as those reflecting significant neurologic abnormalities or requiring further investigations or interventions. In addition, a comprehensive systematic review of the literature was performed, which was conducted in accordance with the PRISMA guidelines. The search included 2 databases (PubMed and Google Scholar) and was completed on May 1st 2023.The search terms included (paediatric) AND (diplopia) AND (emergency).

Results: During the 10‐years study period, of overall 745 patients admitted to ED with AOBD, 62 were children. Accounting for 8.36% of all the visits. Our population consisted of 27 females (43.54%) and 35 (56.45%) males. The mean age was 9.87 years (±4.83). 62 (retrospective analysis) and 590 patients (systematic review), met the inclusion criteria. The majority of the patients had non‐ECs, incidence between 60 and 80%. Among ECs, central nervous system tumours and demyelinating conditions were the most common diagnoses. Although not all the patients with ECs presented with associated sings (54%), most of the patients exhibiting associated signs were found to have an underlying EC.

Conclusions: Most cases of diplopia in children admitted to the ED had non‐ECs underlying conditions. The literature indicates a statistically significant relationship between the presence of associated neurologic signs and ECs.
A simple method for preservation of embryonic rat brain tissue for primary neuron culture
Authors: Pehlivan Çiğdem , Kaleli Humeyra Nur , Sahin Afsun , Hasanreisoğlu Murat
Published: January 2024

Aims/Purpose: In this study we aim to investigate the effect of short‐term storage of embryonic rat brain tissue in Hibernate‐E medium to be used in the isolation of primary neurons for in vitro biocompatibility and electrophysiology tests of retinal and optic nerve prosthesis. Functionally viable neuron cells will be an alternative method for regular dissection from tissue for further experiments.

Methods: Hippocampal tissues from E15‐E17 embryos of Wistar Albino rat were dissecting for primary neuron culture. Half of the tissues were isolated on the same day and used as a control group for further experiments. The test group was stored in a Hibernate‐E medium for 1 week and the same isolation method was performed for the test group. For tissue preservation, half medium replacement with fresh Hibernate‐E medium on the 4th day was enhanced cell viability. Morphology, characterization and synapse formation were determined with immunoflorescence staining.

Results: Comparison of neuronal survival between cultures prepared from stored hippocampi and freshly isolated hippocampi resulted in similar neuronal survival rates in both preparations with cell viability assays. Cell viability rate of hippocampus tissue isolated from rat embryo brain was demonstrated as 96% and cell viability rate of preserved tissue in Hibernate‐E Medium for 7 days was revealed as 90.22% by trypan blue cell viability test (n = 4). Morphological and immunocytochemical characterizations of stored and fresh hippocampal cultures were similar by observing beta‐III Tubulin neuron cytoskeleton biomarker.

Conclusions: As a conclusion, our method has the potential to increase repeatability of primary neuron cultures within 1 week and reduce the number of isolation steps in research. In addition, it will provide a great convenience in the experimental timelines of the researchers and contribute to the reduction of the workload despite any obstacles during primary neuron culture.
Altered corneal structures in form‐deprived highly myopic chicks
Authors: Kang Byung Soo , Leung Tsz‐wing , Vyas Sonal , Ayerakwah Patience , Lin Jia Chun , Liang Yuanyuan , Stell William , Kee Chea‐su
Published: January 2024

Aims/Purpose: Myopia is a leading cause of correctable and preventable vision loss worldwide, but the relationship between myopia development and growth of the anterior segment, particularly the cornea, has not been well established. This study aims to investigate whether experimental induction of myopia influences corneal structures in animals.

Methods: Ten chicks were unilaterally form deprived by covering their right eyes with translucent diffusers at post‐hatching day 6 (P6). Refractive state, corneal shape, and ocular axial dimensions were measured at 4‐day intervals until P18 using a Hartinger refractometer, a custom‐made videokeratography system, and an A‐scan ultrasonographer, respectively. Parameters in treated vs control eyes were compared at the end of treatment. Repeated one‐way ANOVA was used for statistical analysis, and all parameters were expressed as mean ± SD.

Results: At the end of treatment, form‐deprived eyes were myopic (−29.48 ± 8.26D vs. ‐0.61 ± 0.32D) and axially elongated (11.15 ± 0.55 mm vs. 9.51 ± 0.20 mm). At baseline (P6), treated and fellow contralateral eyes had similar corneal power (132.22 ± 6.37D vs. 132.64 ± 5.48D, p = 0.86) and thickness (167.93 ± 6.80 μm vs. 166.43 ± 7.27 μm, p = 0.63), but at P18 form‐deprived eyes had slower corneal flattening and thickening, resulting in significantly steeper (117.73 ± 5.03D vs. 113.22 ± 3.44D, p < 0.05) and thinner corneas (176.80 ± 7.52 μm vs. 192.35 ± 5.62 μm, p < 0.001) than fellow contralateral eyes. Repeated measures correlation analysis further indicated that axial elongation from P6 to P18 was significantly associated with corneal steepening (rrm = 0.77, p < 0.001) and thinning (rrm = −0.69, p < 0.001).

Conclusions: This study provides insights into the impact of form deprivation myopia on corneal structures in juvenile animals. Specifically, the corneas of form‐deprived eyes were steeper and thinner because the natural corneal flattening and thickening processes were decelerated by treatment. Further studies are warranted to reveal the mechanisms responsible for this association between development of refractive error and corneal structure.
P3HT:ITIC polymer based photovoltaic biointerfaces for neural photostimulation
Authors: Kaleli Humeyra Nur , Karatum Onuralp , Pehlivan Çiğdem , Kesim Cem , Yıldız Erdost , Sahin Afsun , Nizamoğlu Sedat , Hasanreisoğlu Murat
Published: January 2024

Aims/Purpose: Optoelectronic neural interfaces have diverse applications in comprehending neural network and treatment of neurodegenerative conditions especially in the field of the vision impairments. We aimed to use the non‐invasive, capacitive photocurrent generation stimulated by near‐infrared light in the biological environment integrating P3HT:ITIC devices to provide neuroprotective and neurodegenerative effects with reducing axonal damage through local repetitive photo‐stimulation.

Methods: In this study, we performed neuron stimulation with the help of ITO/ZnO/P3HT:ITIC photoactive polymer implant placed on an indium tin oxide (ITO) glass. To evaluate the biocompatibility of the P3HT:ITIC devices, CTG cell viability and LDH leak assay were performed on primary nervous and visual system cells including Mio‐M1 and primary astrocytes. Cell specific biomarkers were examined by immunofluorescence staining to demonstrate short‐ and long‐term morphological changes and neural network improvements on both the biointerface and ITO control substrates.

Results: We fabricated NIR‐responsive photovoltaic P3HT:ITIC biointerface with ZnO nanoparticles (NPs) as electron transport layer and P3HT:ITIC thin films as photoactive layer on ITO glass substrates. After evaluation of their stability, we showed that primary neurons, astrocytes and Müller glia cells on the biointerface have high cell viability, low cytotoxicity and preserved cellular network and morphology after 2 weeks of culture condition.

Conclusions: Our study will provide novel solutions to existing problems in electrostimulation devices by exploring capabilities of wirelessly functional, biocompatible organic polymer‐based photoelectric devices with low cost of production. They have a potential in establishing a platform for the development of near infrared light‐controlled electrostimulation treatment, that can improve axonal healing in retina and optic nerve injuries.
Insights into human choroid melanocyte and stromal cells
Authors: Madigan Michele , Wu Chieh‐Lin (Stanley) , Cioanca V. , Conway Robert
Published: January 2024

Aims/Purpose: The human choroid is a complex highly vascular pigmented tissue between Bruch's membrane and the sclera. Its dynamic nature is important for eye homeostasis and for in pathology including macular degeneration and myopia. The stroma comprises heterogeneous cell populations including fibroblasts, melanocytes, immune cells, smooth muscle cells and neurons within a loose collagenous extracellular matrix. We used RNA transcriptome and multimarker immunolabelling of human choroidal melanocytes and tissue to further characterize adult choroidal melanocytes.

Methods: Human choroidal melanocytes were cultured (n = 6 postmortem donor eyes, <18 h delay, UNSW HREC), and used between passage (P) 2 to 5 for RNA transcriptome and multimarker immunofluorescence labelling and confocal microscopy. Sections and flatmounts from central choroid were also compared. Immunolabelling included melanocyte (Tyrosinase, TRYP1, DCT, MelanA) and stromal cell (S1004A, vimentin, α‐smooth muscle actin, CD45) markers.

Results: Cultured melanocytes displayed mostly bipolar morphology with heterogeneous eumelanin density related to donor eye iris colour. Whole transcriptome findings showed enriched melanogenesis genes (high level TYR, PMEL, MITF, TYRP1; MLANA; low level DCT1, MC1R) but not genes reported for RPE (e.g. RPE65), pericytes (e.g. ACTA2) or fibroblasts (e.g. IGF2) confirming melanocyte culture quality. We also found expression for proposed Schwann cell precursors PLP1 and SOX10. Immunolabelling confirmed overall expression of melanogenesis proteins, and subpopulations expressing PLP1 and Sox10, in culture and in choroidal tissue.

Conclusions: Melanocytes and stromal fibroblast are among the most numerous and complex heterogeneous populations within the choroid and our study provides further details on characteristics markers and topography. A possible role for Schwann cell precursors in renewing adult melanocyte populations is intriguing and continues to be investigated.
PGC‐1a inhibition promotes autophagy in induced pluripotent stem cell‐derived retinal pigment epithelial cells generated from age‐related macular degeneration patients
Authors: Hytti Maria , Kauppinen Anu , Skottman Heli , Blasiak Janusz , Kaarniranta Kai
Published: January 2024

Aims/Purpose: Dysfunctional protein clearance, oxidative stress, mitochondrial damage, and chronic inflammation cause retinal pigment epithelial (RPE) cell damage and the development of age‐related macular degeneration (AMD). PGC‐1α can alleviate oxidative stress, is a key player in mitochondrial quality control and could be considered as a treatment target in AMD. Here, we assessed the effect of PGC‐1α inhibition on induced pluripotent stem cell (iPSC)‐derived RPE cells exposed to hydroquinone‐induced oxidative stress.

Methods: iPSC‐derived RPE cells from two neovascular AMD patients or one healthy age‐matched control were cultured for 8 weeks on transwell cell culture inserts until mature. Cells were exposed to the PGC‐1α inhibitor SR‐18292 for 1 h before an exposure to hydroquinone for an additional 4 h. Lactate dehydrogenase (LDH) was measured from collected medium samples to assess cellular viability. Cells were lysed in 3x Laemmli sample buffer for analysis by western blotting or subjected to RNA extraction, followed by RT‐PCR analysis.

Results: Hydroquinone caused a robust increase in LDH release to the medium, which was not modulated by PGC‐1α inhibition. In neovascular AMD‐derived iPSC‐RPE cells, hydroquinone caused an accumulation of p62 and LC3‐II, an effect that was reversed by SR‐18292 pre‐treatment. In control iPSC‐RPE cells, neither hydroquinone nor SR‐18292 affected autophagic markers p62 or LC3. RT‐PCR analysis showed an increase in p62 mRNA levels following hydroquinone exposure in both control‐ and AMD‐derived iPSC‐RPE cells while no change was observed in the RNA levels of LC3B or mTOR.

Conclusions: Increased oxidative stress caused autophagy dysregulation in AMD‐derived iPSC‐RPE cells but not in healthy age‐matched control cells. Interestingly, PGC‐1α inhibition promoted autophagy and the clearance of p62, but further studies are necessary to explore the underlying pathways and the disease‐specific differences observed between healthy and disease‐derived RPE cells.
In situ distribution of markers for stemness, quiescence, proliferation and differentiation in the human cornea and limbus
Authors: Bisevac Jovana , Moe Morten Carstens , Petrovski Goran , Noer Agate
Published: January 2024

Aims/Purpose: Identify the distribution of the most commonly used markers for stemness, quiescence, proliferation, and differentiation in limbal compartments such as human limbal epithelial crypts, posterior and anterior limbus, as well as the central and posterior cornea.

Methods: Corneal‐limbal biopsies from cadaver human donors (n = 3) embedded in paraffin were proceeded for immunohistochemistry fluorescence and examined for stemness/progenitor markers (p63α, SOX9, ABCG2, N‐cadherin), proliferation markers (ki‐67), quiescence marker (CEBPD), differentiation markers (CX43, KRT3, KRT12, KRT13), and epithelial marker (E‐cadherin). Images were obtained by Zeiss Axio Observer. Fluorescent images were obtained using the Zeiss Axio Imager M1 fluorescence microscope (ZEISS, Oberkochen, Germany).

Results: The stemness/progenitor markers p63α and SOX9 were found in basal and suprabasal cells of limbal epithelial crypts and limbal epithelium, whereas the ABCG2 and N‐cadherin were exclusive for limbal basal epithelium in all limbal structures. Proliferation marker Ki‐67 was most abundant in suprabasal layers of the limbus and rarely found in the posterior cornea, while absent in anterior cornea. Quiescence marker CEBPD was positive in the basal cells of both, limbus and cornea. Differentiation markers KRT3 and KRT12 were positive in the whole cornea and intermediate and superficial layers in anterior and posterior limbus, while rarely present in limbal epithelial crypts. However, CX43 was staining almost all suprabasal layers in the limbus as well as basal and suprabasal layers in the cornea. KRT13 was exclusive for superficial layer of the anterior and posterior limbus layers staining conjunctival cells.

Conclusions: Here we identify the localization of the most common markers used to determine the stemness, quiescence, proliferation, and differentiation status to unravel the in situ distribution of these markers in the limbal epithelial crypts, posterior and anterior limbus, as well as the central and posterior cornea. The study accumulated new knowledge about the distribution of these markers and the corneal‐limbal organization.
ON–OFF electroretinogram analysis in patients with negative electroretinograms
Authors: Pojda‐Wilczek Dorota
Published: January 2024

Aims/Purpose: In a healthy population, the flash full‐field electroretinography (ffERG) includes a negative a‐wave and a positive b‐wave. The amplitude of the b‐wave is larger than the a‐wave amplitude in normal patients. In dark‐adapted ERG, the b:a ratio is about 1.6–1.8. The term “negative electroretinogram” is used when the b‐wave amplitude is smaller (negative–negative) or relatively smaller (negative–positive) than the a‐wave amplitude.

This study aims to describe the differences in the ERG of patients with a negative ERG caused by genetic and acquired diseases to help better narrowing down an accurate diagnosis.

Methods: The retrospective study comprised 10 patients aged 5–43 years (4 female, 6 male). ffERG was done according to the ISCEV standards. ON–OFF ERG protocol was additionally used. RETeval portable device (LKC, USA) and sensor strip palpebral electrodes were used.

Results: Negative ERG was found in patients with congenital stationary night blindness (X‐linked, autosomal dominant, autosomal recessive, Oguchi disease), fundus albipunctatus, X‐linked retinoschisis, vitamin A deficiency, vigabatrin toxicity, retinal inflammation. In ON–OFF protocol differences between the function of the ON and OFF bipolar cells in the various diseases are present and will be discussed.

Conclusions: ffERG with ON–OFF protocol should be done in all patients with nyctalopia or inner retina diseases. Detailed analysis of ERG may help to establish the clinical diagnose of retinal disease and to narrow the area of genetic investigation.
Investigating focal macular electroretinogram function for fundus‐related perimetry application
Authors: Suzuki Naoto
Published: January 2024

Aims/Purpose: This study aimed to investigate the utility of focal macular electroretinogram (ERG) function in fundus‐related perimetry (microperimetry) for assessing cryptogenic diseases such as macular dystrophy. The decline in visual sensitivity of the retina was measured using microperimetry, and the retinal layer causing this decline was identified using multifocal ERG.A focal macular ERG function was used for microperimetry instead of multifocal ERG.

Methods: The developed apparatus comprised illumination and photographic optical systems separated by a mirror with a hole, a microperimetry optical system and an ERG optical system separated by a 45° cold mirror. It also consisted of an Edmund infrared camera EO‐50231, a lens, a halogen lamp, an objective lens, four double convex lenses, two aperture stops, a mirror, a 12.1‐inch high brightness (2000 cd/m2) monitor and an artificial eye. Its electrical measuring equipment included a differential amplifier, a high‐pass filter, a 50‐Hz notch filter and two non‐inverting amplifiers. Moreover, the equipment consisted of the National Instruments' I/O device USB‐6216, a shielded connector block, plate electrodes, an electromagnetic shield sheet and the LabVIEW 2018 software for data retrieval. To perform the focal macular ERG, a DynaScan 49‐inch ultrahigh brightness (3500 cd/m2) liquid crystal display (LCD) was prepared.

Results: The ERG software could display three stimulus spot circles with diameters of 5°, 10° and 15° on the ultrahigh brightness LCD. Additionally, a function for adjusting the size of the stimulus spot circle was added as the diameter was changed from 1° to 15°. The focal macular ERG was able to measure a wave, b wave and photopic negative response (PhNR). It was found that certain small waves on the b wave were confirmed with high probability as oscillatory potentials (OPs), while one positive wave similar to the d wave was confirmed sometimes; however, the c wave was not confirmed.

Conclusions: It can be concluded that when not only the a wave, b wave and PhNR but also the OPs and d wave are confirmed, the focal macular ERG function can identify the retinal layer causing visual alterations at specific points throughout the retina.
Texture analysis shows interocular retina asymmetries in women not existing in men
Authors: Bernardes Rui , Nunes Ana , Ferreira João , Guimarães Pedro , Serranho Pedro , Castelo‐Branco Miguel
Published: January 2024

Aims/Purpose: Recent research has demonstrated that retinal texture is a valuable source of biomarkers for neurodegeneration. Previous studies have examined the layer thickness of the neuroretina in women and men as measured from optical coherence tomography (OCT) data. The effect of sex‐based retinal interocular differences remains relatively unexplored. This study looked into texture metrics from OCT data of healthy adult individuals to determine if interocular differences are related to sex.

Methods: Grey‐level co‐occurrence matrix features were computed from mean‐value fundus images from the six layers of the neuroretina. These features were tested separately for group mean differences between the female and male participants' right and left eyes. A pairwise correlation analysis was first performed to exclude similar features. The non‐correlated features were tested for normality, and a paired‐sample t‐test or a signed rank test was applied accordingly to evaluate the group mean differences. Due to the many pairwise tests, three different pairwise correction methods were applied: Bonferroni, Benjamini–Hochberg, and the False Discovery Rate.

Results: Initial uncorrected results showed that interocular retinal texture asymmetries were mainly present in women and with a larger effect size than in men. After correction, except for the highly conservative Bonferroni method, the results revealed that texture differences were only present in the female group, while the eyes of men were similar.

Conclusions: Our work suggests that structural patterns in the right and left eyes manifest differently in females and males, raising the question of why such differences occur and how they might vary over the lifespan, both in healthy individuals and in patients diagnosed with neurodegenerative disorders. In addition, it further emphasizes the need for accurate control in studies that use both eyes.
Retinal response to two commercially available contact lenses for myopia control
Authors: Amorim‐de‐Sousa Ana , Fernandes Paulo , Queirós António , Meijome José Manuel González
Published: January 2024

Aims/Purpose: Myopia control contact lenses (CLs) have shown optimistic results in eye growth retention in children. However, it is still unknown the retinal mechanisms of defocus detection. This study evaluated the electrophysiological response of the retina with two myopia control CLs, compared to single‐vision CLs.

Methods: High‐contrast visual acuity (VA) and the retinal activity of 16 eyes (16 subjects, 27.5 ± 5.7 years, 12 female) with myopia (from −0.75 to −6.00 D, astigmatism >1.00 D) were assessed with two single‐vision CLs (Omafilcon A – SVo – and Filcon 5B – SVf) and two myopia control CLs (dual‐focus – DF, Omafilcon A – and extended‐depth‐of‐focus – EDOF, Filcon 5B). The global‐flash multifocal electroretinogram (gf‐mfERG) was recorded with the Reti‐port/scan21 (Roland Consult) with a 61‐hexagons stimulus in physiological pupil conditions. The implicit time (milliseconds) and response density (nV/deg2) of the direct (DC) and induced (IC) components were compared between CLs of matching material.

Results: All CLs showed similar VA (p > 0.050). The implicit times did not show statistically significant differences. DF showed higher response density of both DC and IC components at all retinal areas, with a statistically significant difference in the parafoveal DC component (difference of 2.77 [6.23–1.44] nV/deg2, p = 0.038), compared with the SVo. EDOF showed a higher response density of about 13.31 [23.88–3.85] nV/deg2 (p = 0.032) in the foveal IC component, compared with the SVf. The remaining retinal areas did not show statistically significant differences.

Conclusions: The retina seems to respond differently to distinct CL's optical designs. The two myopia control CLs increased the electrophysiological response of the retina, but with different effects, without affecting the implicit time of the response. Multifocal contact lenses with peripheral defocus induce different foveal and parafoveal activities that might be involved in the mechanism of myopia control.
Contrast threshold recovery after bleaching during cone‐mediated mesopic adaptation: The effect of test conditions
Authors: Remis‐Gonzalez Melisa , Moreira‐Estebaranz Carolina , Gavilán Beatriz Sánchez , Liébana Javier Álvarez , Cedrun‐Sanchez Juan , Puell María
Published: January 2024

Aims/Purpose: To determine the optimal luminance conditions and the staircase procedures for evaluating the time course of macular contrast sensitivity recovery after photobleaching in order to decide the best protocol to assess cone‐mediated mesopic adaptation.

Methods: The dynamics of contrast threshold (CT) recovery following photopigment bleach were measured psychophysically for five minutes in twenty‐four healthy adults (23.7 ± 3.7 years old). The stimuli used were sine‐wave gratings of low‐spatial frequency (1 cycle‐per‐degree). In each subject, six tests were performed, combining three luminance levels (0.1, 1.0, and 10 cd/m2) and two modified staircase procedures (3‐down/1‐up and 2‐down/1‐up) to estimate CTs. The test order was randomized, conducted in two visits, with a 15‐min washout period between tests. Outlier detection techniques were applied to verify the integrity of the sample. Non‐linear exponential‐based optimization was adopted to fit CT recovery functions to estimate the time constant (τ, seconds) of cone sensitivity recovery and the final CT (CTf, log units). Classical and heteroscedastic ANOVA analyses were performed to assess the effect of test conditions.

Results: The 2‐down/1‐up staircase allowed for denser point sampling of CTs measurements than the 3‐down/1‐up. Under the lowest luminance test condition, the CT recovery was modelled by bumpier functions, for both staircases procedures, than the other luminance levels. Mean cone τ increased (21.7, 42.5, and 72.0 seconds (p < 0.001)) and CTf worsened (−1.99, −1.85, and − 1.47 log units (p < 0.001)) as luminance level decreased. The best fit (median R2 = 0.87) was achieved under 1 cd/m2 mesopic luminance conditions. There were no statistically significant differences in mean cone τ and CTf between the two staircases procedures.

Conclusions: An intermediate mesopic light level and a 2‐down/1‐up staircase provided the best protocol for assessing cone‐mediated mesopic adaptation.
Development of a cone‐mediated dark adaptation test on a smartphone
Authors: Gavilán Beatriz Sánchez , Remis‐Gonzalez Melisa , Moreira‐Estebaranz Carolina , Pundlik Shrinivas , Puell María
Published: January 2024

Aims/Purpose: Dark adaptometry is considered a useful tool for investigating retinal neurodegenerative diseases. While it has been demonstrated that the loss of rod photoreceptors occurs before the loss of cones, foveal cones are also impacted during the initial stages of age‐related macular degeneration. Our aim was to develop a test to assess cone‐mediated dark adaptation (DA) based on the MOBILE‐DA smartphone app.

Methods: The MOBILE‐DA smartphone app for testing rod‐mediated DA was modified to assess cone‐mediated DA. Using an Android smartphone, and a 3° diameter achromatic flashing stimulus centered on the fovea, the measurements were made using an adaptive staircase of 0.007 cd/m2 level up – 0.009 cd/m2 level down. In a dark room, the smartphone was placed 40 cm from the subject, and the luminance thresholds were measured monocularly for 5 min following almost complete photopigment bleaching using a long‐duration light exposure (60 seconds). Luminance Threshold (LT) recovery functions were fitted to an exponential decay model to determine the time constant (τ, seconds) of cone sensitivity recovery and final cone LT.

Results: The cone‐mediated DA measured by the smartphone app resulted in τ of 91 ± 15 seconds; final cone LT of −2.29 ± 0.10 log cd/m2, and R2 of 0.96 ± 0.02. The time constant and final threshold values obtained through this app were comparable to those obtained through other established techniques.

Conclusions: The smartphone app for evaluating cone‐mediated dark adaptation proved effective in tracking the rapid changes in luminance threshold that take place during this process. These findings suggest that the MOBILE‐DA app is well‐suited for measuring cone‐mediated dark adaptation.
A meta‐analysis of surgical treatments for childhood glaucoma
Authors: Lee Yun Jeong , Kim Young Kook
Published: January 2024

Aims/Purpose: To assess the comparative efficacies of surgical interventions for childhood glaucoma (CG).

Methods: Through electronic database searches up to August 7, 2022, randomized controlled trials (RCTs) involving surgical interventions for CG were identified. A meta‐analysis was conducted to compare the surgical interventions: Conventional partial trabeculotomy ([CPT] control), 240‐degree trabeculotomy, Illuminated microcatheter‐assisted circumferential trabeculotomy (IMCT), Viscocanalostomy, Visco‐circumferential‐suture‐trabeculotomy, Goniotomy, Laser goniotomy, Kahook dual blade ab‐interno trabeculectomy, Trabeculectomy with mitomycin C, Trabeculectomy with modified scleral bed, Deep sclerectomy, Combined trabeculectomy‐trabeculotomy with mitomycin C, and Baerveldt implant. The main outcome measures were postoperative 6‐month mean intraocular pressure (IOP) reduction and surgical success rate. The mean differences (MDs) or odds ratios (ORs) were obtained using a random‐effects model, and the efficacies were ranked by P‐score.

Results: Sixteen (16) RCTs were eligible for inclusion in the analysis, involving 710 eyes of 485 participants and 13 surgical interventions, which formed a 14‐node network. IMCT was superior to CPT in both IOP reduction (MD [95% CI], −3.10 [−5.50 to −0.69]) and surgical success rate (OR [95% CI], 4.38 [1.61 to 11.96]), while the MD and OR comparing the other surgical interventions with CPT were not statistically significant. Moreover, the IMCT was ranked as the most efficacious surgical intervention for success rate (P‐score = 0.777).

Conclusions: This meta‐analysis revealed that IMCT is more effective than CPT and might be the most efficacious surgical intervention for CG.
Comparison of a preservative‐free bimatoprost 0.01% ophthalmic gel with a preserved bimatoprost 0.01% ophthalmic solution: A phase III, randomized, multicentre, 3‐month study
Authors: Negrete Francisco José Muñoz , Topouzis Fotis , Oddone Francesco , Nisslé Sylvie , Rokicki Dariusz , Januleviciene Ingrida , Harasymowycz Paul , Stalmans Ingeborg
Published: January 2024

Purpose: The aim of this study was to evaluate the intraocular pressure (IOP)‐lowering efficacy and safety of a novel preservative‐free bimatoprost 0.01% ophthalmic gel (PFB 0.01% gel) compared with preserved bimatoprost 0.01% (PB 0.01%) in patients with ocular hypertension (OHT) or glaucoma.

Methods: This was a randomized, multicentre (90 centres), investigator‐masked, 3‐month treatment duration, phase III trial. Following a 7‐week run‐in/washout period, patients were randomized to receive once‐daily PFB 0.01% gel (n = 236) or PB 0.01% (n = 249) for 3 months. The primary efficacy measure was change from baseline IOP at Week 12 at 3 timepoints. Noninferiority was based on a predetermined criteria (upper 95% confidence interval margin of 1.5 mmHg at all timepoints). Safety evaluations included conjunctival hyperaemia, ocular symptoms and occurrence of adverse events (AEs).

Results: Mean change from baseline in IOP at Week 12 in the PFB 0.01% gel and PB 0.01% were − 9.72 ± 2.97 and − 9.47 ± 3.06 mmHg, respectively at 8 am, −9.41 ± 3.03 and − 9.19 ± 3.12 mmHg at 10 am, and − 8.99 ± 3.36 and − 8.54 ± 3.44 mmHg at 4 pm. Noninferiority of PFB 0.01% gel to PB 0.01% was demonstrated at Week 12 at all timepoints. The percentage of patients experiencing a worsening from baseline in conjunctival hyperaemia score was lower with PFB 0.01% gel compared to PB 0.01% at Week 12 (18.3% vs 30.4%, respectively). Ocular symptoms upon instillation were less frequent in the PFB 0.01% gel group compared to the PB 0.01% group at Week 12 for irritation/burning (12.7% vs 21.2%, respectively), itching (5.4% vs 10.4%) and eye dryness feeling (7.3% vs 14.3%). The most frequent treatment‐related AE was hyperaemia, reported in 15 (6.4%) patients in the PFB 0.01% gel group and 26 (10.4%) patients in the PB 0.01% group.

Conclusions: PFB 0.01% ophthalmic gel had the same efficacy in lowering IOP as PB 0.01%, demonstrated less aggravation of conjunctival hyperaemia at Week 12 and less ocular symptoms upon instillation.
Long term intraocular pressure fluctuation and epiretinal membrane in patients with glaucoma or glaucoma suspect
Authors: In Jung Kyoung , Ryu HeeKyung , Park Chan Kee
Published: January 2024

Aims/Purpose: The associations between ERM and glaucoma were suggested in several studies. In an animal model undergoing intermittent IOP elevations, a reactive gliosis, a phenotype of ERM, was found in the optic nerve head. We investigated the association between intraocular pressure (IOP) fluctuation and idiopathic ERM in patients with glaucoma or glaucoma suspect.

Methods: In this retrospective study, a total of 84 patients with glaucoma or glaucoma suspect were included. Among them, forty one patients had no ERM and forty three patients had ERM. Long‐term fluctuation of IOP was defined as the standard deviation (SD) of IOP at all visits. Patients were divided into two groups according to the median value of SD of IOP: the low IOP fluctuation group and high IOP fluctuation group. Among patients with available heart rate variability (HRV) data, the relationship between the HRV parameter and IOP fluctuation was analysed.

Results: Patients with ERM was older and had higher IOP fluctuation and higher proportion of having history of cataract surgery and greater macular thickness (p = 0.018, 0.049, 0.013, < 0.001). The high IOP fluctuation group showed higher proportion of patients with ERM (62.5%) than the low IOP fluctuation group (36.4%, p = 0.028). In the multiple logistic analysis, higher IOP fluctuation group were associated with the presence of ERM (p = 0.047). Among patients with ERM, eyes with stage 3 or 4 ERM had worse visual field defects based on mean deviation than those with stage 1 or 2 ERM (p = 0.025). The high IOP fluctuation group showed higher level of low frequency HRV, an index of sympathetic cardiac control than the low IOP fluctuation group (p = 0.027). Intereye comparison in eyes with ERM and the fellow eyes without ERM, eyes with ERM (2.2 ± 0.9 mmHg) had higher fluctuation of IOP than those without ERM (2.0 ± 0.8 mmHg, p = 0.029).

Conclusions: In conclusion, long‐term IOP fluctuation had the relevance to idiopathic ERM in patients with glaucoma or glaucoma suspect. In glaucoma patients with ERM, more advanced stage ERMs were associated with worse visual field damage. Further studies are needed to determine if long‐term IOP fluctuation affects the progression of glaucoma and ERM.