bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinguishing clinical and etiological profile of occlusive retinal vasculitis in a referral center in Tunisia, North Africa
Authors: Malouch Issam eddine , Abroug Nesrine , Khairallah Molka , Belghith Yassine , Attia Sonia , Khairallah Moncef
Published: December 2022

Purpose: To compare clinical profile and visual outcomes of occlusive versus non‐occlusive retinal vasculitis (RV).

Methods: A retrospective comparative study.

Results: 284 patients were enrolled, including 124 patients with occlusive RV (ORV) and 160 patients with nonocclusive RV (NORV). Patients with ORV were older (p ≤ 10‐3), predominantly male (p ≤ 10‐3), with less bilateral involvement (31.5% vs. 53.4%; p ≤ 10‐3). Infectious RV was more frequently diagnosed in the ORV group than in the NORV group (48.8% vs. 32.9%, p = 0.006). Behçet disease and ocular tuberculosis were the leading causes of ORV. Idiopathic RV, Behçet disease, and sarcoidosis were the most common causes of NORV. Independent predictive factors of poor visual outcome were worse baseline visual acuity in both groups (p = 0.006 and p ≤ 10‐3, respectively), and retinal haemorrhages (p = 0.048) and optic atrophy (p = 0.040) in the ORV group.

Conclusions: Occlusive and non‐occlusive RV have distinctive clinical and etiological profile.

References

1. Agarwal A, Karkhur S, Aggarwal K, Invernizzi A, Singh R, Dogra MR, et al. Epidemiology and clinical features of inflammatory retinal vascular occlusions: pooled data from two tertiary‐referral institutions: Inflammatory retinal vascular occlusion. Clin Experiment Ophthalmol. janv 2018;46(1):62–74.

2. Mir TA, Reddy AK, Burkholder BM, Walsh J, Shifera AS, Khan IR, et al. Clinical Features and Incidence Rates of Ocular Complications in Patients With Retinal Vasculitis. Am J Ophthalmol. juill 2017;179:171–8.
Tear proteome profile in eyes with keratoconus after intracorneal ring segment implantation or corneal crosslinking
Authors: Goñi Nahia , Martínez‐Soroa Itziar , Ibarrondo Oliver , Azkargorta Mikel , Elortza Felix , Galarreta David , Bidaguren Aritz , Juaristi Leire , Acera Arantxa
Published: December 2022

Purpose: Intracorneal Ring Segment (ICRS) and Corneal collagen Crosslinking (CXL) are widely used treatments in keratoconus (KC) disease, but the alterations they cause in biomechanical mediators in the cornea, are still poorly understood. The aim of this study was to analyse the tear proteome profile before and after treatments to identify biomarkers altered by surgery.

Methods: An observational, prospective, case–control pilot study was conducted, analysing tear samples from KC patients by nano‐liquid chromatography‐mass spectrometry (nLC‐MS/MS). Patients with KC who underwent ICRS surgery (n = 4), CXL (n = 4), and healthy subjects (CT, n = 4) were included in this study. Clinical parameters were measured and tear samples were collected before and 18 months after surgery. Proteins with ≥2 expression change and p‐value <0.05 between groups and times were selected to study their role in postoperative corneal changes.

Results: These analyses led to the identification of 447 tear proteins. In comparisons between the two surgical groups and CTs, the biological processes that were altered in KC patients at baseline were those that were dysregulated as a consequence of the disease. Among the biological processes seen to be altered were: immune responses, cytoskeleton components, protein synthesis, and metabolic reactions. When comparing the two treatment groups, A‐kinase anchor protein 13 (AKAP‐13) was the most overexpressed protein before and after surgery in CXL group.

Conclusions: The changes observed in tears after 18 months postoperatively could be due to the treatments performed and the pathology. Among the deregulated proteins detected, AKAP‐13 deserves special attention for its involvement in corneal thinning, and for its strong overexpression in the tears of patients with more active KC and faster disease progression. However, it should be kept in mind that this is a pilot study conducted on a small number of patients.
Structural and functional exploration of the retinal vasculature in HANAC syndrome associated with a novel intronic COL4A1 mutation
Authors: Faure Céline , Castrale Cindy , Benabed Anaïs , Cognard Pauline , Lezé Romain , Gérard Marion , Louapre Céline , Paques Michel
Published: December 2022

Purpose: Mutations of the COL4A1 gene may cause hereditary angiopathy with nephropathy, aneurysms and muscle cramps (HANAC) syndrome. The vascular structure and function of patients with HANAC is poorly known. Here, we report a family with HANAC syndrome associated to a previously unreported mutation in COL4A1. The structure and function of retinal vessels were detailed by adaptive optics ophthalmoscopy (AOO) and optical coherence tomography (OCT) angiography.

Methods: Clinical data from six affected individuals from a single family over two generations were collected. Imaging charts including conventional fundus imaging, OCT‐angiography and AOO in static and dynamic (flicker) mode were reviewed. DNA sequencing was done in the proband.

Results: DNA sequencing of the proband revealed a heterozygous deletion of COL4A1 (NM_001845) at position 1120 in the intron 20 resulting in the loss of splicing donor site for exon 20 (c.1120 + 2_1120 + 8del heterozygote). Four had arterial hypertension, and three had kidney dysfunction, one of which under dialysis. Examination of retinal vessels showed that all patients had retinal arteriolar tortuosity which peaked in precapillary arterioles but spared capillaries and veins. Wall‐to‐lumen ratio of arteries was within normal limits, that is, lower than expected for hypertensive patients. Several foci of arteriolar irregularities were noted I the oldest patients. In three affected subjects, evaluation of the neurovascular coupling showed a high flicker‐induced vasodilation (from 6% to 10.8%; n < 5%).

Conclusions: Structural and dynamic analysis of retinal vessels in a HANAC family bearing a novel intronic COL4 mutation showed reduced parietal thickness, arteriolar irregularity and increased dilatory response to flicker light. This affected as well non tortuous arteries, suggesting that HANAC causes diffuse microvascular dysfunction. Our findings may help to better understand end‐organ damage related to HANAC.
Expression and activation of MMP10 in retinal pigment epithelium cell lines and plasma levels in age‐related macular degeneration patients
Authors: Gonzalez‐Zamora Jorge , Hernandez Maria , Bezunartea Jaione , Recalde Sergio , Zuazu Idoia Belda , Orduña Maite Moreno , Fernandez‐Robredo Patricia , Layana Alfredo García
Published: December 2022

Purpose: The aim of the study is to evaluate the role of MMP10 in AMD at the cellular level and in human samples.

Methods: To determine expression in retinal pigment epithelium (RPE) cells, immunofluorescence labeling and western blotting (WB) and relative quantification PCR (RQ‐PCR) were performed in ARPE‐19 and human RPE primary cells (hRPE). To evaluate the effect of oxidative stress conditions on MMP10 expression and activation, cells were subjected cells exposed to H2O2 at 800 μM during 48 h. To evaluate the levels of MMP10 in AMD patients, the plasma concentration measured by ELISA in an age‐ and sex‐matched 1:1 case–control cohort (104 patients).

Results: MMP10 is expressed in ARPE‐19 cells and hRPE cells under basal conditions. ARPE‐19 cells exposed to showed a prominent increase in MMP10 expression in the immunofluorescence labeling. WB analysis of MMP10 under basal conditions in the supernatant and cell lysate of ARPE‐19 and hRPE cells have a marked expression of MMP10 contained intracellularly and present a measurable concentration of extracellular MMP10. H2O2 exposition seems to activate the protein generating two visible bands in WB. RQ‐PCR shows a significant increase in MMP10 mRNA transcription over time under oxidative stress conditions. Comparison of mean MMP10 plasma showed no statistically significant differences. A statistically significant negative correlation between age and MMP10 plasma levels was observed in the control while no apparent correlation was found in the AMD group.

Conclusions: Our study demonstrates that MMP10 is expressed in human epithelial cells and is overexpressed and activated under oxidative stress conditions. This increase in expression by RPE observed in cells does not correlate with an increase in plasma concentration in patients with AMD, however, in contrast to what is observed in controls, there is no decrease in its systemic concentration with age as opposed to what occurs in control patients. The data suggest that MMP10 may play a role in the development of AMD and future experiments are needed to explore this possibility.
Characterization of Charles bonnet syndrome in leber hereditary optic neuropathy patients
Authors: Nguyen Hong‐An , Kreimei Mohammad , Poincenot Lissa , Lalonde Melanie , Karanjia Rustum
Published: December 2022

Purpose: Charles Bonnet Syndrome (CBS) is a condition involving visual hallucinations as a result of vision loss, but it is not well characterized nor routinely assessed for. Some patients with Leber's Hereditary Optic Neuropathy (LHON) experience CBS, but there is limited published data. This is the first study screening for and characterizing CBS in a large cohort of the LHON patient population.

Methods: A recently validated French‐Canadian CBS screening questionnaire was adapted to an online bilingual (English‐French) format, tailored to LHON patients (Cantin et al. CJO, 2019;54:323‐7). The 59‐item questionnaire was distributed to numerous mailing lists, online communities and social media platforms consisting of LHON patients. Quantitative and qualitative response data was used for cross‐sectional analysis.

Results: A total of 169 affected LHON patients completed the questionnaire with 70% screening positive for CBS. Of the participants who screened positive for CBS, 58% were male and 85% were less than 65 years old. 55.1% were affected by the 11778G > A mutation, 13.6% by 14484 T > C, 14.4% by 3460G > A, 7.6% by other mutations and 9.3% by an unknown mutation. In addition, 41.5% of these participants have been diagnosed with LHON for more than 10 years while 38% have been diagnosed for <5 years.

Conclusions: Our results yielded a high proportion of LHON patients screening positive for CBS (70%), indicating the condition may be a lot more common than previously suspected, and only a minority of LHON patients are being adequately assessed and managed for the condition. There is also an indication that their CBS tends to be long‐lasting and can be associated with various negative health outcomes. Overall, this study provides a better understanding of the prevalence of CBS in LHON and the need for proactive discussions by health care providers.

References

1. Cantin S, Duquette J, Dutrisac F, Ponton L, Courchesne M, de Abreu Cybis W, et al. Charles Bonnet syndrome: development and validation of a screening and multidimensional descriptive questionnaire. Canadian Journal of Ophthalmology 2019;54:323–7. https://doi.org/10.1016/j.jcjo.2018.05.008.
Outcomes from a new surgical procedure in lower eyelid reconstruction: Marginal approach to releasing the lid with closure handling technique (MARCH technique)
Authors: De Ribot Anna March , de Ribot Francesc March
Published: December 2022

Purpose: To present a new surgical procedure for lower eyelid reconstruction.

Methods: We have included several patients with carcinomas in their lower eyelids to perform its excision and reconstruction using this new surgical technique. Here we describe the procedure and present the surgical details and outcomes.

Results: In cases where the defect involves up to 66% of the lower eyelid with at least around 17% of remnant lateral lower margin respected, the MARCH technique would be a more conservative approach, with very promising results that would encourage us to use it as the first surgical step.

Conclusions: Skin cancers are especially harmful due to local invasion and surgical iatrogenic morbidity. The recurrence may be high, implying challenging surgical management depending on the prior surgery performed which, in eyelids sometimes, may mean sacrifying periosteum or tarsus. With this technique, minimal damage to perilesional healthy tissues is caused, providing good resources for the future.
Characterization of Descemet membrane of Fuchs endothelial corneal dystrophy by chromatic confocal microscopy
Authors: Vaïtinadapoulé Hanielle , Zhiguo H. E. , HAMRI Alina , Thomas Justin , GAIN Philippe , Mascarelli Frederic , THURET Gilles ,   French Fuchs Study Group FFSG
Published: December 2022

Purpose: Fuchs corneal endothelial dystrophy (FECD) causes chronic corneal edema and vision loss, and accounts for more than 50% of keratoplasty indications in occidental countries. The Descemet membrane (DM) gradually thickens because of extracellular matrix deposition and round excrescences named guttae accumulate. Chromatic confocal microscopy (CCM) is on optical device that analyses the nanotopography of surfaces.

Aim: to study the feasibility of CCM technology to characterize guttae in FECD.

Methods: Descemetorhexis of approximately 8 mm in diameter were obtained during endothelial grafts in 11 patients with FECD and control corneas were obtained from 3 donor corneas. The DM were fixed in 0.5% paraformaldehyde immediately after dissection. The CCM analysis was performed at room temperature on surfaces of 400 x 400 μm to characterize the DM with and without guttae. We measured positive and negative heights (peaks and valleys) relative to the mean altitude, as well as their distribution by asymmetry coefficient.

Results: CCM resolution allowed to map nanotopography of the DM of FECD patients and controls. The surface of DM control was flat and homogeneous with maximum positive and negative heights of 1.07 ± 0.09 μm and 1.05 ± 0.07 μm, respectively. The height distribution was uniform with an asymmetry coefficient of 0.002 ± 0.23 μm, reflecting a Gaussian distribution (npeaks = nvalleys). The surface of FECD membranes was completely altered with a maximum peak of 6.05 ± 1.49 μm, up to 5.7 times higher than the control. The height distribution was disturbed with asymmetry value of 1.61 ± 0.79 μm (npeaks > nvalleys) and a maximum valley height (3.09 ± 0.79 μm) that was half that of the peak one.

Conclusions: CCM is a promising technology to quantitatively characterize the 3D organization of the DM surface. CCM can be used to classify the different types of surface lesions of the FECD corneas and to follow evolution of DM alteration at different stages of the disease.
Correlation between systemic and ocular pressure‐related factors with anatomic parameters in patients with diabetes
Authors: Dimitrova Galina , Petkovska Ivana , Kemera Dushan , Minova Natasha Nedeska , Taner Hasan , Ljubic Antonela , Lazarevska Lidija
Published: December 2022

Purpose: Previous studies suggested pressure‐related factors to be involved in the pathogenesis of diabetic retinopathy. In this study, we aim to correlate systemic and ocular pressure‐related factors with anatomic parameters in control subjects and in patients with and without diabetic retinopathy (DR).

Methods: We included 31 control subjects, 32 patients with diabetes mellitus (DM) without DR and 37 patients with DR. The following parameters were evaluated: best corrected visual acuity, intraocular pressure (IOP) (mmHg), body mass index (BMI), mean blood pressure (MBP) (mmHg), HbA1c (%), estimated cerebrospinal fluid pressure (CSFP) (mmHg), trans‐laminar pressure difference (TLPD) (mmHg), ocular perfusion pressure (OPP) (mmHg), axial length (AL) (mm), spherical equivalence (SE) (D) and OCT parameters (optic disk area (mm2), optic cup/disk (C/D) ratio, retinal nerve fibre layer thickness (NFLT) (μm), foveal thickness (μm), average macular thickness (AMT) (μm)). We used either Pearson's or Spearman' coefficient of correlation depending on data distribution. Results were considered statistically significant with p value < 0.05.

Results: Presence of DM had a significant low association with CSFP (Rs = 0.28, p = 0.006), BMI (Rs = 0.24, p = 0.019) and with AL (Rs = −0.27, p = 0.011). CSFP had a significant low association with SE (R = −0.38, p = 0.002) and with NFLT (R = 0.27, p = 0.046) only in patients with DM. TLPD had a significant low association with optic C/D ratio in control subjects (R = 0.45, p = 0.014) and a significant low association with NFLT in patients with DM (R = −0.35, p = 0.007). In patients with DM, IOP had a significant low association with MBP (R = 0.26, p = 0.032), BMI (R = 0.29, p = 0.017) and CSFP (R = 0.29, p = 0.017), whereas in control subjects IOP had a significant moderate association with optic C/D ratio (R = 0.57, p = 0.001) and a significant low association with AMT (R = −0.43, p = 0.016).

Conclusions: Systemic and ocular pressure related factors have different correlation patterns in patients with DM than in control subjects.
Is the anatomy of the macula different in individuals with dyslexia?
Authors: Medina José Javier García , Bascuñana‐Mas Nieves , Molina Celia Gómez , Velázquez Elena Rubio , Zanón‐Moreno Vicente , Duran Maria Dolores Pinazo , Sobrado‐Calvo Paloma , del‐Rio‐Vellosillo Monica
Published: December 2022

Purpose: The purpose of this research was to compare the thickness of different retinal layers between dyslexic subjects and controls at the macula by means of optical coherence tomography (OCT).

Methods: Each patient underwent a complete ophthalmic examination including macular OCT in both eyes. The thickness of the fovea, four sectors of the parafovea and four sectors of the perifovea were obtained according to the Early Treatment Diabetic Retinopathy Study protocol in the following 13 segmentations: complete retina, outer retina, inner retina, retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), INL + OPL + ONL, IPL + INL, OPL + ONL and ganglion cell complex (RNFL + GCL + IPL). The results of the right and left eyes were independently compared between groups.

Results: The thickness in all the four sectors of the parafovea was found significantly higher in the right and in the left eyes in the dyslexic group in the following segmentations: complete retina, inner retina, middle retinal layers and OPL + ONL. Several macular sectors were also thicker in IPL + INL, INL, IPL and ONL in dyslexia. In contrast, no thickness differences between both groups were found in any of the sectors of RNFL, GCL, GCC, or outer retina in any eye.

Conclusions: Anatomy of the macula is different in dyslexic and normoreader subjects in middle retinal layers, especially in the parafovea. This fact suggests that the macula may play an important role in the development of dyslexia.
Vogt‐Koyanagi‐Harada disease following a serology‐proven Bartonella henselae retinitis: A case report
Authors: Fekih Khawla , Hager Ben Amor , ahmed mahjoub , meriem slimen , Sana Khochtali , Attia Sonia , Ksiaa Imen , Khairallah Moncef
Published: December 2022

Purpose: To report a case of Vogt‐Koyanagi‐Harada (VKH) disease following a serology‐confirmed bartonella henselae retinitis.

Methods: A single case report.

Results: A 41‐year‐old female patient presented with a central scotoma in her right eye (RE). Fundoscopic examination showed a focal retinitis with a macular star in the RE. Work‐up revealed positive bartonellosis serology. The patient was treated with oral azithromycine and oral steroids during 4 weeks with subsequent healing of the retinitis lesion. Three months after initial presentation, the patient complained of loss of vision in both eyes. Ophthalmological examination showed a best‐corrected visual acuity (BCVA) of 20/200 on both eyes, with a bilateral granulomatous panuveitis with bilateral multifocal exudative retinal detachment. Results of multimodal imaging were consistent with the diagnosis of acute VKH disease.

Given the history of positive bartonellosis serology, the patient was treated with doxycycline (200 mg/day) for 6 weeks in association with intravenous methylprednisolone for 5 days followed by oral steroids and progressive tapering. At three‐month follow‐up, BCVA improved to 20/20 in both eyes associated with resolution of clinical and structural OCT changes.

Conclusions: Our case suggests that bartonella henselae infection might be a non‐previously reported infectious trigger of VKH disease in genetically predisposed patients. Alternatively, bartonella henselae infection might manifest with panuveitis mimicking VKH disease.
Ocular symptoms in confirmed COVID‐19 patients: A local survey of mid and South Essex trust, England
Authors: Asghar Muhammad Saad , Akram Haseeb , Chandra Aman
Published: December 2022

Purpose: There have been several reports of COVID‐19 affecting the eyes. This retrospective study aimed to investigate which eye symptoms are commonly seen in adults who have previously tested positive for COVID‐19.

Methods: Patients were identified based on the primary diagnosis of COVID‐19 on admission to three hospitals in the Mid & South Essex Trust, admitted during April–May of 2020 & Jan–Feb 2021. Ethical approval was obtained and these patients were sent a retrospective questionnaire after discharge. The questionnaires inquired about the presence of eye symptoms experienced before, during and after their covid illness. It also included questions about covid admission duration and hospitalization details. Thirty patient responses were returned and analysed.

Results: Ten patients out of 30 respondents (33.33%) developed worsening of pre‐existing eye conditions: Most commonly Tiredness (70%), itchiness(50%), dryness(50%), Grittiness (30%), Redness (30%), Burning (30%), Pain (20%), Discharge (20%) & formation of a Lump/Bump (20%). Ten patients out of 30 respondents (33.33%) also developed new eye symptoms. Most commonly being Tiredness(40%), Vision change(30%), Pain (20%), Grittiness (20%).

Conclusions: The majority of the patients experienced ocular symptoms suggestive of a viral conjunctivitis. Such clinical features in patients presenting to the Eye Unit could represent a manifestation of COVID‐19 illness. It could be useful to use these data to consider covid PCR testing in patients who present to eye units with viral ocular presentations. These data may be relevant to any future viral pandemic.
The safety of ranibizumab and bevacizumab on senescent retinal pigment epithelial cells
Authors: Shin Jeongah , Hwang Gyudeok
Published: December 2022

Purpose: Retinal pigment epithelial (RPE) cells in patients with age‐related macular degeneration are presumably senescent. This study investigated the effects of ranibizumab and bevacizumab on the viability of senescent RPE cells.

Methods: Premature senescence of human RPE (ARPE‐19) cells was induced by exposure to low‐dose pulsed H2O2 stress for 5 days and confirmed with senescence‐associated 𝛽‐galactosidase (SA‐𝛽‐gal) staining. After treatment with clinical doses of ranibizumab and bevacizumab, the MTT [3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide] assay and flow cytometry were used to determine cell viability. A caspase 3/7 assay, cell cycle analysis, SA‐𝛽‐gal staining, and in vitro wound healing assay were also performed to investigate the effects of the drugs on senescent ARPE‐19 cells.

Results: Ranibizumab and bevacizumab did not have deleterious effects on apoptosis, cell viability, additional senescence, or the migration capacity of senescent RPE cells.

Conclusions: Clinical dosages of ranibizumab and bevacizumab do not produce significant cytotoxicity in senescent RPE cells.

Reference

1. Klein R, Klein BE, Jensen SC, Meuer SM. The five‐year incidence and progression of age‐related maculopathy: the Beaver Dam Eye Study. Ophthalmology. 1997; 104: 7–21.
Considerations for the management of low vision in retinitis pigmentosa with tunnel vision: A case series
Authors: Latifah Latifah , Dewi Nadia , Anny Sulistiyowati
Published: December 2022

Purpose: This study discusses considerations for the management of low vision in retinitis pigmentosa patients with tunnel vision.

Methods: Diagnoses were based on history taking, anterior segment examination, retinal examination with 78D indirect ophthalmoscope, and ancillary testing. Baseline central macular thickness was measured with spectral‐domain optical coherence tomography (Zeiss Cirrus HD‐OCT 5000). The visual field was measured with the Humphrey field analyser. The retina's electrical activity was measured with an electroretinogram (ERG). Contrast sensitivity was measured with the Pelli‐Robson chart.

Results: We discuss three cases of retinitis pigmentosa: An 18‐year‐old male, a 26‐year‐old female, and a 47‐year‐old male with bilateral RP and CME. The diagnosis of RP was based on the clinical features of night‐blindness, narrowing visual field, with characteristic funduscopic findings, which are arteriole attenuation, waxy disc pallor, and “bone spicule” appearance. All three cases indicated tunnel vision and a decrease in scotopic response of ERG results. Decreased photopic response was shown in the second and third case. Decreased contrast sensitivity was found in all cases, especially in the third case. Although all cases showed CME in OCT findings, only the third case had visual acuity less than 6/6 and was treated with spectacles. The management of tunnel vision in all of the cases comprises best visual acuity correction, orientation and mobility (O&M) training, and Trifield glasses, if available.

Conclusions: Tunnel vision in patients with RP considered a low‐vision aid (Trifield glasses) with an O&M training to extend their visual field. In the RP‐CME, patient whose visual acuity is less than 6/6 binocularly was given spectacles alongside with therapy for CME secondary to RP.
Patterns of sclero‐uveitis in a referral center in Tunisia, North Africa
Authors: Malouch Issam Eddine , Abroug Nesrine , Belghith Yassine , Slimene Meriem Haj , Attia Sonia , Khairallah Moncef
Published: December 2022

Purpose: To describe the demographics and clinical characteristics of anterior scleritis associated with uveitis in a referral center in Tunisia.

Methods: The charts of twenty patients (20 eyes) diagnosed with sclero‐uveitis at Fattouma Bourguiba University Hospital, Monastir, Tunisia, presented between January 2015 and April 2022, were retrospectively reviewed. Detailed ophthalmic examination and fundus photography were performed in all patients. Mean follow‐up period was 28.4 months. Patients with keratitis or posterior scleritis were excluded.

Results: There were eight women and 12 males patients with a mean age of 34.8 years. All patients presented with ocular pain. Mean initial best‐corrected visual acuity (BCVA) was 20/80 (range, 20/2000–20/25).There was an associated anterior uveitis in 80% of cases and panuveitis in 20%. Clinical findings at presentation included nodular scleritis in five eyes (25%) and scleromalacia perforans in four eyes (20%). Idiopathic sclero‐uveitis accounted for almost 55%. Identified causes of sclerouveitis included rheumatoid arthritis in four eyes (20%), tuberculosis in three eyes (15%), granulomatosis with polyangiitis in two eyes (10%), sarcoidosis in one eye (5%) and then one case after mRNA 1273 vaccine (5%). Ocular complications included pupillary seclusion in 25% of cases and vision loss in 10% of patients. Mean final BCVA was 20/100 (range, 20/4000–20/32). Treatment modalities of non‐infectious scleritis included indomethacine in 14 patients (82.3%), systemic corticosteroid in seven patients (41.1%) and immunosuppressant or biological agent in five patients (29.4%).

Conclusions: Our results provide useful information about the patterns and etiologies of sclerouveitis. The leading causes of sclerouveitis include mainly rheumatoid arthritis and tuberculosis. An infectious cause should be always ruled out.
Anterior segment optical coherence tomography for the detection and management of early keratoplasty complications
Authors: Ferchichi Molka , Meriem Ouederni , Ammar Hamdi Ben , Zaienb Gharbi , Fehmy Nafaa , Cheour Monia
Published: December 2022

Purpose: This study aimed to assess the contribution of anterior segment optical coherence tomography (AS‐OCT) in the detection of early postoperative complications following penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) in order to guide their management.

Methods: A single‐center, prospective study, designed to evaluate the postoperative results of 42 eyes who had PK (39 eyes) and DALK (3 eyes) for various diagnoses. Complications occurring between the first and 7th day after surgery were recorded. AS‐OCT was performed to assess central corneal thickness (CCT), Descemet's membrane (DM) position, graft‐host junctions (GHJ), and iridocorneal angle (ICA) opening.

Results: Early postoperative complications were detected in 4 eyes (9.5%). Among them, 2 eyes (patients 1 and 2) had PK for corneal perforation, and 2 eyes (patients 3 and 4) had DALK for keratoconus. Patient 1 had an early graft ectasia. Corneal thinning was first detected on the 6th postoperative day by CCT measurement on AS‐OCT. He underwent a second PK with a favourable outcome. Patient 2 had persistent corneal edema on the 4th postoperative day. AS‐OCT revealed graft steps at the GHJ. After surgical revision, the graft became clear and the GHJ were well‐apposed on AS‐OCT. Patient 3 had important graft edema (CCT 1005 μm) secondary to DM detachment diagnosed on the first postoperative day with AS‐OCT. She was treated with an intracameral air injection leading to the reattachment of DM and regression of the edema. Patient 4 had on the first postoperative day a pupillary block successfully managed with a peripheral iridotomy leading to the reopening of the ICA seen on AS‐OCT.

Conclusions: AS‐OCT is a non‐contact and reproducible imaging tool that proved to be useful to identify early postoperative complications after keratoplasty and to guide their management. It allows for a quantitative and objective assessment of the anterior segment behind a usually non‐transparent corneal graft.
Repeatability of quantitative measurements of anterior segment analysis with swept‐source AS‐OCT in dry eye, ocular surface disease and healthy eyes
Authors: Recchioni Alberto , Domínguez‐Vicent Alberto , Venkataraman Abinaya Priya , Wallace Graham , Rauz Saaeha
Published: December 2022

Purpose: Dry eye and ocular surface disease (OSD) are the most common causes of eye discomfort with up to 50%1 of the global population affected. Anterior segment optical coherence tomography (AS‐OCT) is essential to diagnose and track ocular surface changes. This study aims at assessing the precision of a modern swept source AS‐OCT in OSD vs healthy control.

Methods: Five clinical groups were included: G1 = Sjögren's syndrome (n = 46); G2 = Ocular Mucous Membrane Pemphigoid, Graft‐versus‐Host Disease, etc. (n = 58); G3 = Meibomian Gland Disease (n = 47); G4 = Miscellaneous (Neurotrophic, Exposure, Transplant, etc.) (n = 36); G5 healthy controls (n = 41). Three consecutive measurements using a radial scan mode were collected using the AS‐OCT Casia2 (Tomey, Japan) and the repeatability limits (RLs) were calculated. The following parameters were obtained: anterior chamber depth (ACD), AC width (ACW), angle opening distance (AOD) and angle recess area (ARA) both at 250, 500 and 750 μm, angle to angle (ATA), central thickness apex (CTapex), lens vault (LV), trabecular iris angle (TIA) and trabecular iris‐space area (TISA) both at 250, 500 and 750 μm. Dry eye metrics such as OSDI® questionnaire, fluorescein break‐up time (FBUT), tear meniscus height (TMH), conjunctival inflammation (INFLCONJ) and ocular surface staining (OSS) were considered.

Results: The higher RLs values were observed within the G4 cohort considering AOD (0.28, 0.29, 0.36, 0.35, 0.43 vs G5 0.18, 0.21, 0.18, 0.20, 0.26 mm),ARA (0.08, 0.10, 0.16, 0.18, 0.25, 0.27 vs. G5 0.06, 0.06, 0.09, 0.10, 0.14, 0.15 mm2), CTapex (66.12 vs. G5 13.55 μm), TIA (33.90, 22.57, 14.55, 20.02 vs. G5 30.94, 18.31, 9.44, 14.76 degrees) and TISA (0.06, 0.07, 0.14, 0.15, 0.23, 0.24 vs. G5 0.04, 0.05, 0.08, 0.09, 0.12, 0.14 mm2). G1 cohort reported the worst dry eye metrics (OSDI 52.90 ± 20.58 score, FBUT 3.51 ± 2.36 s, TMH 0.10 ± 0.07 mm, INFLCONJ 1.07 ± 1.78 score, OSS 4.27 ± 2.35 score).

Conclusions: This is the first study to consider anterior segment analysis repeatability limits in OSD vs healthy cohorts with the AS‐OCT Casia2. Despite G1 cohort reported the worse dry eye metrics, the higher repeatability limits were observed in the G4 Miscellaneous group.

Reference

1. Stapleton, F. et al. TFOS DEWS II Epidemiology Report. Ocular Surface 15, 334–365, doi:10.1016/j.jtos.2017.05.003 (2017).
Ex vivo model for the measurement of intraocular pressure and force of injection during the administration of hollow microneedles in porcine sclera
Authors: Glover Katie , Mishra Deepakkumar , Thakur Raj
Published: December 2022

Purpose: The current gold standard treatment option for posterior segment diseases such as age‐related macular degeneration is the delivery of drug into the vitreous cavity by intravitreal injection. This method is, however, associated with several issues including low patient compliance and the risk of adverse effects [1]. Microneedles (MNs), designed to deliver their payload into the sclera, offer a minimally invasive means of providing localized drug delivery to the eye, providing a potentially more patient‐friendly alternative. MNs for ocular drug delivery have gained significant interest in recent years; however, for clinical acceptability, safe values for parameters such the injection force and changes in intraocular pressure (IOP) are critical. This work investigated the effects that changing MN design parameters (e.g., bevel angle, needle length and needle gauge) had on both the force of penetration (FoP) and depth of penetration (DoP) achieved in ex vivo porcine sclera at clinically relevant locations. The model used a pressure transducer to allow for real‐time monitoring of IOP over the injection procedure.

Methods: Stainless steel hollow microneedles (ssHMNs) were fabricated from conventional hypodermic needles, with a range of bevel angles (30–75°) cut in triplicate using Wire Electrical Discharge Machining. Needle heights were adjusted as required using 3D‐printed adapters. To assess FoP and DoP, ssHMNs were inserted into ex vivo porcine sclera with images being captured using optical coherence topography. IOP changes during the injection procedure were monitored in real‐time using a pressure transducer.

Results: ssHMNs were shown to partially penetrate the ex vivo porcine sclera. Average values obtained for FoP and DoP were shown to be dependent on sclera location. Peak IOP values were observed upon scleral penetration, with these being lower with smaller needle sizes. Similarly, average FoP values were found to decrease for higher gauge needles and smaller bevel angles.

Conclusions: This work demonstrates the effects of changing design parameters of ssHMNs on the FoP and DOP achieved in ex vivo porcine sclera, as well as changes in IOP.

Reference

1. “Stimuli sensitive ocular drug delivery systems,” in Drug Targeting and Stimuli Sensitive Drug Delivery Systems, 2018, pp. 211–270.
Topical sevoflurane corneal toxicity: in vitro study
Authors: Cejudo Raquel Maroto , Encalada Denisse Michelle Espinosa , Valenciano Carlos Cava , Juarez Sango Mónica Gómez‐ , Picazo Maria Gomez , Pretel Fernando Andrés
Published: December 2022

Purpose: The purpose of the study is to investigate the cytotoxic effect of sevoflurane (SF) and povidone‐iodine (PI) on cultured rabbit corneal epithelial cells in vitro.

Methods: We evaluated the cytotoxic effect of a 5 min exposition of SF, PI and balanced saline solution (BSS) using an in vitro rabbit corneal cell culture model (Short‐Time Exposure Test Method). In order to quantify cytotoxicity MTT assay was employed. Repeated exposition of SF was evaluated as well as cell viability after different recovery times (30 min, 60 min and 1 h). Statistical results were obtained with Kruskal‐Wallis test and Conover post‐hoc test.

Results: The median of cell viability of SF was 85.29%, PI 0.52% and BSS 97.29%, with statistically significant differences between them (p = 0.005). After a 5 minute recovery, the median of cell viability for SF was 87.77%, 74.48% after 30 minutes and 76.66% after 60 minutes. After a double exposition it was 70.59%, with no statistically significant differences between single and double exposition (p = 0.18).

Conclusions: No corneal toxicity of SF was observed, in contrast with PI. Cellular damage did not change with longer recovery time or double exposition to SF.

References

Sevoflurane (SF) has been proved recently to have analgesic/antimicrobial effects. (1, 2) We believe of interest to study the effect of SF in the ocular surface. As there is no literature about this topic, in vitro studies are required before in vivo tests.

1. Chu CC, Wu SZ, Su WL, Shieh JP, Kao CH, Ho ST, et al. Subcutaneous injection of inhaled anaesthetics produces cutaneous analgesia. Can J Anesth Can Anesth. 2008;55(5):290–4.

2. Manuel Gerónimo Pardo, María Martínez Serrano, Ángel Martínez Monsalve, Juan Luis Rueda Martínez. Usos Alternativos del Sevoflurano: Efecto Analgésico Tópico. Rev Electrónica AnestesiaR [Internet]. 2012 [cited 2019 Apr 15];4(5). Available from: http://revistaanestesiar.org/index.php/rear/article/view/373
Different behaviour of Müller cells according to their location in the retina: Possible relation with the differential susceptibility of retinal ganglion cells in glaucoma
Authors: Pereiro Xandra , Ruzafa Noelia , Ambrósio António Francisco , Santiago Ana Raquel , Vecino Elena
Published: December 2022

Purpose: Glaucoma is a neurodegenerative disease and the leading cause of irreversible blindness in the world. Increased intraocular pressure (IOP) is considered a major risk factor. When visual problems are first detected in patients with glaucoma, half of the retinal ganglion cells (RGCs) have already died, principally in the peripheral retina. Müller glia (MG), which are the main macroglial cells in the retina, play prominent physiological and pathological roles. The change of MG to a reactive phenotype initiates signalling cascades that may serve a neuroprotective role, but may also promote damaging effects on RGCs. Our main hypothesis is that MG exert an important role in RGCs death in glaucoma, being the MG in the periphery the most sensitive to intraocular pressure, promoting the death of RGCs.

Methods: Survival of RGCs was analysed by immunocytochemistry in porcine primary co‐cultures of RGCs and MG from central and peripheral retina under control and elevated hydrostatic pressure (EHP) conditions. The conditioned media (CM) from MG primary cultures from central and peripheral retina were collected and analysed by mass spectrometry to identify and quantify proteins in all experimental conditions.

Results: We demonstrated that in control condition MG secret neuroprotective factors, and in EHP MG contribute to RGC death. MG from central retina are less sensitive to EHP since RGCs survival further decrease in co‐culture with MG from peripheral retina. Moreover, stretch‐activated nonselective TRPV4 cation channels present in MG are differently activated by the pressure depending of their location within the retina. Proteomic analysis from CM of MG revealed differential protein expression levels, being more pronounced in the CM from MG from peripheral retina under EHP. The proteins identified are mainly associated to apoptosis, oxidative stress, inflammation and angiogenesis.

Conclusions: The different sensitivity of the RGCs to IOP in glaucoma could be related with the different activation of neighbouring MG.
Validation of the CD11c‐DTR transgenic mouse as a model to study neuroimmune interactions in the cornea
Authors: Frutos‐Rincón Laura , Rincón‐Frutos Maria José , Acosta M. Carmen , Gallar Juana
Published: December 2022

Purpose: CD11c‐DTR+ mice have a transgene encoding for a simian diphtheria toxin (DT) receptor under the CD11c promoter that makes dendritic cells (DCs) sensitive to DT, which causes DC depletion. Preliminary results using this mouse suggest that there is a functional interaction between DCs and corneal sensory nerves, as DC depletion modifies nerve activity and nociceptive behaviour. The aim of this work was to validate the CD11c‐DTR+ mouse model proving that the observed effects are not due to the DT itself, using littermates negative for the transgene and therefore resistant to DC depletion by DT.

Methods: CD11c‐DTR+ and CD11c‐DTR‐ mice (5 months, both sexes) were used. Both groups received single or repetitive (every 2 days for 8 days) subconjunctival injections of DT or its vehicle (PBS). Basal tearing (in mm) was measured using phenol red threads placed in the temporally side of the eye for 30 s in isoflurane‐anaesthetised mice. To quantify spontaneous eye pain, the eye closure ratio was calculated by dividing the height by the width of the lid opening measured in photographs of freely moving animals. Nerve terminal impulse (NTI) activity of corneal cold thermoreceptor endings was recorded ex vivo in superfused eyes; spontaneous and stimulus‐evoked activity was explored.

Results: Basal tearing was higher in DT‐injected CD11c‐DTR‐ animals, especially after repetitive injections (Day 0: 2 ± 0.16 mm vs. day 2: 2.8 ± 0.37 mm vs. day 8: 4.7 ± 0.36 mm, n = 5, p ≤ 0.001, RM ANOVA). Repetitive PBS injections caused similar effects in CD11c‐DTR+ and CD11c‐DTR‐ mice tearing (DTR−: 4.7 ± 0.36 mm, n = 5 vs. DTR+: 3.7 ± 1.48 mm, n = 3, p = 0.399, t‐test). No signs of spontaneous pain were observed in DT‐injected CD11c‐DTR‐ mice (Day 0: 0.91 ± 0.01 vs. 48 h: 0.93 ± 0.01 vs. day 8: 0.95 ± 0.01, n = 5, p = 0.065, RM ANOVA). No significant differences were found in spontaneous and stimulus‐evoked NTI activity recorded after repetitive injections of DT in CD11c‐DTR− mice or PBS in CD11c‐DTR+ mice.

Conclusions: CD11c‐DTR+ mice are a valid model to study neuroimmune interactions. DT has no effects on pain behaviour or NTI activity of animals lacking the DT receptor. The changes in tearing appear to be consequence of the subconjunctival injection process per se.

Reference

PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103
Neuronal and vascular segregation reveals the impact of systemic hypertension on peripapillary RNFL thickness in diabetic patients without diabetic retinopathy
Authors: Schmetterer Leopold , Wong Damon , Yow AiPing , Tan Bingyao , Hussain Rahat , Chua Jacqueline
Published: December 2022

Purpose: Diabetes (DM) and hypertension (HTN) are common comorbidities in the elderly and can cause damage to the retina, such as neurodegeneration and vascular impairment. The purpose of this study was to determine the impact of HTN on the axonal versus the vascular components of the RNFL thickness in patients with DM without clinical diabetic retinopathy.

Methods: Subjects were divided into three groups: healthy controls, 2. patients with DM only, and 3. patients with both DM and HTN. Automated segmentation of peripapillary RNFL is performed, and vascular component is excluded from the segmented RNFL to obtain the thickness measurements and vascular metrics. RNFL with (original) and without the vascular component (corrected) were compared between subjects with diabetes and healthy controls.

Results: A total of 279 eyes were included: 182 eyes in controls group, 31 eyes in DM only, and 66 eyes in DM + HTN. The mean original RNFL thickness was significantly thinner in DM + HTN (−3.85 μm, p = 0.014) when compared to controls (103.9 ± 10.1 μm). This relationship between the groups increased significantly when the vascular component is excluded from the RNFL increased (−4.6 μm, p = 0.002). Retinal vessel density was increased in patients with hypertension (14.83 ± 0.32 μm) versus controls (13.97 ± 0.18 μm, p = 0.019) and was correlated with original RNFL thickness (r = 0.189, p = 0.001), but not with corrected RNFL (r = −0.044, p = 0.462). There was no difference in the RNFL thickness between DM only and controls when using either conventional or novel OCT approaches (−3 μm, p ≥ 0.100).

Conclusions: The present data indicate that reduced RNFL thickness in diabetic patients without diabetic retinopathy is to a large degree related to impact of hypertension. Changes in peripapillary RNFL thickness as measured with commercial OCT systems may either be the consequence of retinal nerve fibres or reflect changes in retinal vasculature. Accounting for retinal vasculature emphasized the greater decrease in RNFL in HTN individuals than conventional OCT method.
Calculations of mean ocular perfusion pressure before and after exercise are conditioned by the formula used
Authors: Gene‐Morales Javier , Gené‐Sampedro Andrés , Bueno‐Gimeno Inmaculada , Colado Juan C.
Published: December 2022

Purpose: Blood pressure is a key parameter associated with ocular health and glaucoma. Additionally, brachial blood pressure serves to calculate ocular perfusion pressure. The main aim was to evaluate differences between the most used formulas to calculate mean brachial arterial blood pressure and the effects that physical exercise may have in this parameter.

Methods: Fifteen physically active, healthy subjects (9 male 6 female, 24.07 ± 3.65 years) voluntarily performed a 15‐minute protocol consisting of combined exercise including, mobility, bodyweight exercises, running, dynamic stretching, and three sets of barbell back squat at low intensities. The formulas compared were 1) diastolic blood pressure (DBP) + 1/3 * (systolic blood pressure [SBP] ‐ DBP); 2) DBP + 0.412 * (SBP – DBP); 3) DBP + (0.333 + (0.0012 * heart rate)) * (SBP ‐ DBP); 4) DBP + (25.361 + 0.047 * heart rate + 0.163 * DBP) * (SBP ‐ DBP); 5) (SBP * DBP) ^ 1/2. A two‐way analysis of variance evaluated the effect of the exercise and the formula used to calculate the mean blood pressure.

Results: Significant effects of the exercise (F(1, 14) = 88.66, p < 0.001, η2 = 0.86), formula used (F(1.06, 14.86) = 250.23, p < 0.001, η2 = 0.95), and their interaction (F(1.37, 19.11) = 54.75, p < 0.001, η2 = 0.80) were observed in the resulting values. The post‐hoc results showed significant differences between most of the formulas both preexercise and postexercise.

Conclusions: The results presented suggest that caution should be applied when using indirect formulas to estimate mean brachial arterial pressure. Future research should objectively evaluate mean blood pressure with a direct method to find the most reliable formula. Meanwhile, this study is published to raise awareness on the importance of choosing one or other methods when aiming to estimate with formulas physiological parameters related to ocular health.