Ocular Trauma Characterization in a Reference Emergency Eye Centre in Colombia (FOSCAL).

BACKGROUND: Ocular trauma is one of the most important causes of ocular morbidity and inadequate visual acuity in developed and developing countries. In some countries, eye trauma is the leading cause of monocular blindness. Studies conducted in developing countries like Colombia suggest that there is a lack of awareness of preventive measures. In Colombia, there is no countrywide ocular trauma registry. The purpose of the present study is to describe and analyse characteristics of ocular trauma at a tertiary ophthalmology emergency department in Colombia. PATIENTS/METHODS AND MATERIAL: Patients who consulted or were referred to the ophthalmologic emergency department of FOSCAL due to eye injuries between March 1, 2022, and January 10, 2023, were included in this cross-sectional study. RESULTS: Of 1 957 patients, 2 088 eyes were included. Men comprised 78.5% of the patients, the median age was 36 years, and 75.0% lived in urban areas. The median latency between trauma and ophthalmology consultation was 21.8 hours. Of the eyes, 1 805 (88.4%) had suffered mechanical or mixed (mechanical plus burn) trauma. Of the injuries, 87.5% were unilateral. In terms of the circumstances, 45.9% of injuries occurred during working or educational activities (in 85.6% of these cases, without eye protection), 28.2% in home accidents, and 14.0% in transportation situations. According to the Birmingham Eye Trauma Terminology System (BETT), 1 735 eyes (91.1%) were closed globe injuries, and 49 eyes (2.7%) were open globe injuries. Fifty eyes (2.8%) could not be categorised according to BETT at the initial consultation and were classified as "still to be determined". In the Ocular Trauma Score (OTS), 85.8% were category 5. Of the ocular burn cases, 93.0% were categorised as grade I according to the Roper Hall classification. CONCLUSIONS: In line with global literature, a much higher proportion of men than women sought consultation for ocular trauma. The findings suggest a need for improvement in the referral process from institutions with the lowest level of care. Lack of awareness about eye protection is an issue. Surgical exploration or additional tests may be necessary for precise injury classification. We therefore propose adding a "still to be determined" category to the BETT initial classification. These cases may be reclassified later, thus improving the accuracy of OTS calculation.

Determination of progressive endothelial cell loss after posterior chamber phakic intraocular lens implantation.

Comments about endothelial cell loss after posterior chamber phakic intraocular lens are provided, with a particular emphasis on the importance of determining progressive postoperative cell density reduction, excluding that related to surgical trauma.

Effectiveness and Safety of Non-Invasive Neuromodulation for Vision Restoration: A Systematic Review and Meta-Analysis.

We carried out a systematic review and meta-analysis to determine the effectiveness and safety of non-invasive electrical stimulation (NES) for vision restoration. We systematically searched for randomised controlled trials (RCTs) comparing NES with sham stimulation, for vision restoration between 2000 and 2022 in CENTRAL, MEDLINE, EMBASE, and LILACS. The main outcomes were as follows: visual acuity (VA); detection accuracy; foveal threshold; mean sensitivity as the parameter for the visual field; reading performance; contrast sensitivity (CS); electroencephalogram; quality of life (QoL), and safety. Two reviewers independently selected studies, extracted data, and evaluated the risk of bias using the Cochrane risk of bias 2.0 tool. The certainty in the evidence was determined using the GRADE framework. Protocol registration: CRD42022329342. Thirteen RCTs involving 441 patients with vision impairment indicate that NES may improve VA in the immediate post-intervention period (mean difference [MD] = -0.02 logMAR, 95% confidence intervals [CI] -0.08 to 0.04; low certainty), and probably increases QoL and detection accuracy (MD = 0.08, 95% CI -0.25 to 0.42 and standardised MD [SMD] = 0.09, 95% CI -0.58 to 0.77, respectively; both moderate certainty). NES likely results in little or no difference in mean sensitivity (SMD = -0.03, 95% CI -0.53 to 0.48). Compared with sham stimulation, NES increases the risk of minor adverse effects (risk ratio = 1.24, 95% CI 0.99 to 1.54; moderate certainty). The effect of NES on CS, reading performance, and electroencephalogram was uncertain. Our study suggests that although NES may slightly improve VA, detection accuracy, and QoL, the clinical relevance of these findings remains uncertain. Future research should focus on improving the available evidence's precision and consistency.

Safety of intracameral application of moxifloxacin and dexamethasone (Vigadexa®) after phacoemulsification surgery.

BACKGROUND: Intracameral antibiotics, such as moxifloxacin and cefuroxime, are safe to corneal endothelial cells and effective prophylaxis of endophthalmitis after cataract surgery. Corneal endothelial cells decrease in density after cataract surgery. Any substance used in the anterior chamber may affect corneal endothelial cells and lead to a greater decrease in density. This study wants to determine the percentage of endothelial cell loss after cataract extraction by phacoemulsification with off-label intracameral injection of moxifloxacin and dexamethasone (Vigadexa®). METHODS: An observational retrospective study was performed. The clinical records of patients undergoing cataract surgery by phacoemulsification plus intracameral injection of Vigadexa® were analyzed. Endothelial cell loss (ECL) was calculated using preoperative and postoperative endothelial cell density. The relation of endothelial cell loss with cataract grade using LOCS III classification, total surgery time, total ultrasound time, total longitudinal power time, total torsional amplitude time, total aspiration time, estimated fluid usage, and cumulative dissipated energy (CDE) was studied using univariate linear regression analysis and logistic regression analysis. RESULTS: The median loss of corneal endothelial cells was 4.6%, interquartile range 0 to 10.4%. Nuclear color and CDE were associated with increased ECL. ECL>10% was associated with age and total ultrasound time in seconds. CONCLUSIONS: The endothelial cell loss after the intracameral use of Vigadexa® at the end of cataract surgery was similar to the reported in other studies of cataract surgery without the use of intracameral prophylaxis for postoperative endophthalmitis (POE). This study confirmed the association of CDE and nuclear opalescence grade with postoperative corneal endothelial cell loss.

Phakic iris-claw intraocular lens: calculations of power and long-term endothelial cells loss.

A correction about phakic intraocular lens power calculation process, as it was stated by Li, Song & Song, is provided. It is explained that this calculation is based on the Van der Heijde formula and not on biometric formulas. A comment about the mechanisms of late endothelial cell loss following phakic intraocular lenses is done.

Genetics vs chronic corneal mechanical trauma in the etiology of keratoconus.

Both genetic and environmental factors have been considered to play a role in the etiology keratoconus. Eye rubbing, and more recently eye compression due to sleeping position, have been identified to be highly related to the condition, and are present in a high percentage of patients. Today, the predominant model is that these factors can provide the "second hit" necessary to generate the condition in a genetically susceptible individual. In addition, the extremely high prevalence in Arab populations, where endogamy could play a role, the high concordance rate in monozygotic twins, and the presence of family history of the condition between 5 and 23% of cases, support a genetic influence. Segregation analysis studies suggest that keratoconus is a complex non-Mendelian disease. Results from linkage analysis, next generation sequencing studies and genome-wide association studies also have suggested that genetic factors are involved in the condition. Recently, it has been proposed that mechanical trauma (i.e. eye rubbing or eye compression at night), is a sine quanon condition for the onset of keratoconus, and quite possibly its only cause. There are various arguments for and against this hypothesis. Indeed, it is possible, as initially suggested around 55 years ago, that the term "keratoconus" include diverse phenotypically similar conditions, which are actually of different etiology.

Long-term endothelial cell loss with the iris-claw intraocular phakic lenses (Artisan®).

PURPOSE: To evaluate the endothelial cell loss in patients with iris-claw phakic lenses (Artisan®) in a long-term follow-up. METHODS: We analyzed the medical records of patients who had undergone iris-claw phakic lens implantation and who had at least 5 years of follow-up. RESULTS: We included 67 eyes with myopic errors (follow-up 9.6 ± 3.0 years) and 10 eyes with mixed astigmatism or hyperopic errors (follow-up 8.8 ± 2.5 years). The mean total endothelial density loss at the last follow-up visit was 18.5% ± 17.0% and 10.5% ± 12.3%, respectively. 29.9% of the eyes in the myopic group and 20% in the hyperopic group lost more than 25% of the preoperative endothelial cell density. During the postoperative follow-up period, 60.8% of the eyes in the myopic group and 40% of the eyes in the hyperopic group lost a higher percentage than the expected physiological loss. Two eyes in the myopic group (3.0%) had a final cell density of less than 1200 cells/mm2. None of the variables studied had a statistically significant association with the percentage of annual endothelial loss in the postoperative period. Three phakic lenses were explanted: two by cataract and one by cataract and severe decrease of the endothelial density (862 cells/mm2). CONCLUSIONS: There is a significant endothelial cell loss in a low percentage of the eyes with Artisan® lenses in the long term, and it can decrease to critical levels. Periodic endothelial density evaluations are required for these patients. The selection criteria of surgical candidates could be reevaluated.

Indications and techniques of corneal transplantation in a referral center in Colombia, South America (2012-2016).

PURPOSE: To describe the indications and techniques of corneal grafting in a tertiary institution in a middle-sized city in Colombia. METHODS: A retrospective review of surgical reports and medical records of patients undergoing keratoplasty from January 2012 to December of 2016. RESULTS: A total of 346 eyes from 316 patients were included. The first three indications for keratoplasty were: bullous keratopathy (BK) with 46.2% of the cases, active infectious keratitis (22.3%) and the group of corneal dystrophies and degenerations, including Fuchs' endothelial dystrophy (9%). Keratoconus was in the sixth place (4.9%). 73.3% of the procedures were penetrating keratoplasties (n = 255), 21.7% posterior lamellar (n = 75) and 3.5% anterior lamellar (n = 12). While in 2012, 25 cases of endothelial grafts were performed, only 13 were done in 2016. CONCLUSIONS: BK was the first cause of keratoplasty with almost half of the cases, and keratoconus was relegated to sixth place with less than 5%. In comparison, in a study from eye banks from the US, BK was the second and keratoconus was the third indication for corneal grafts. The frequency of endothelial lamellar techniques in our institution decreased from 2012 to 2016. This could have been related to both the long time that the patients had to be on a waiting list, which made them unsuitable candidates for this technique, due to stromal fibrosis, and to the fact that surgeons of our institution had less experience with posterior endothelial grafting than with penetrating keratoplasties.

Comparison of three optical biometers: IOLMaster 500, Lenstar LS 900 and Aladdin.

PURPOSE: To evaluate the results of optical biometry using the IOLMaster 500, Lenstar LS 900 and Aladdin in eyes with cataract. METHODS: In 231 eyes of 152 patients with cataract, the measurements of 3 different biometers were retrospectively compared. Paired comparisons were performed for axial length (AL), mean keratometry (mean K) and anterior chamber depth (ACD). RESULTS: In only 197 of the 231 eyes (85.3%), it was possible to obtain reliable measurements of AL with all the three devices. It was not possible to determine AL in 16 eyes (6.9%) with Lenstar LS 900; in 19 eyes (8.2%) with Aladdin; and in 20 eyes (8.6%) with IOLMaster 500 possibly related to the severity of lens opacification (the corneas had good transparency in the eyes included in the study). There was a statistically significant difference in AL between IOLMaster 500 and the remaining two biometers (P = 0.03). However, the amount of difference was considered clinically not significant (0.04 mm). The mean keratometry (mean K) was determined in 203 eyes (87.9%) with all the three devices. Differences in mean K were between - 0.1 and 0.06 Diopters (D), which were considered neither statistically (P > 0.05) nor clinically significant. The anterior chamber depth (ACD) was determined in 197 eyes (85.28%) with all the three biometers. The differences between the three devices (0.03 to 0.13 mm) were not statistically significant and considered also clinically not significant. CONCLUSIONS: There were no clinically significant differences between these 3 biometers in AL, mean K and ACD.

Association of IL-13 rs20541 and rs1295686 variants with symptomatic asthma in a Saudi Arabian population.

OBJECTIVE: Interleukin 13 (IL-13) plays a critical pro-inflammatory role in asthma. Several single nucleotide polymorphisms (SNPs) are associated with asthma susceptibility in specific populations; however, further replicative studies in other ethnic groups are mandatory. METHODS: The association between IL-13 SNPs rs762534, rs20541, rs1295686, and rs1800925 (risk alleles A, A, T, and A, respectively) and asthma predisposition in a Saudi Arabian cohort was examined via a case-control cross-sectional study. RESULTS: The frequencies of alleles between asthmatics and control populations were significantly different for rs20541 and rs1295686 SNPs (p < 0.001), whereas the frequencies of genotypes between asthmatics and controls were significantly different only for rs20541. The association of the risk (minor) alleles with asthma was examined using the dominant genetic model. Individuals with at least one copy of the risk alleles A (for rs20541) and T (for rs1295686) had significantly greater odds of being asthmatic (OR = 2.13, 95% CI = 1.39-3.26, p < 0.0001; OR = 1.69, 95% CI = 1.12-2.54, p = 0.008) relative to their most common homozygous genotypes. On the other hand, the minor A alleles for rs762534 and rs1800925 were not significantly associated with asthma risk. Regarding haplotype association analysis, individuals with at least one copy of the minor "risk" allele for both rs20541 and rs1295686 (CATG and CATA, respectively) had greater odds of being asthmatic relative to CGCG haplotype; however, this trend was not statistically significant (p > 0.3). CONCLUSIONS: IL-13 minor T and A alleles for rs1295686 and rs20541, respectively, were associated with significantly higher risk of asthma in the Saudi Arabian population.

Giant intrastromal cleft in corneal hydrops.

A 15-year-old male patient with corneal hydrops and a giant intrastromal cleft (pseudocyst) successfully received medical treatment with topical prednisolone, hypertonic saline solution and ocular hypotensive eyedrops. Anterior segment optical coherence tomography (OCT) was used as an auxiliary tool for assessing the response to treatment during follow-up time (33 months).

Th-17 regulatory cytokines IL-21, IL-23, and IL-6 enhance neutrophil production of IL-17 cytokines during asthma.

BACKGROUND: In a subset of severe asthma patients, chronic airway inflammation is associated with infiltration of neutrophils, Th-17 cells and elevated expression of Th-17-derived cytokines (e.g., interleukin [IL]-17, IL-21, IL-22). Peripheral neutrophils from allergic asthmatics are known to express higher IL-17 cytokine levels than those from healthy subjects, but the regulatory mechanisms involved are not well understood. We hypothesize that Th-17 regulatory cytokines could modulate IL-17 expression in neutrophils. METHODS: Peripheral blood neutrophils isolated from asthmatics were stimulated with IL-21, IL-23, and IL-6 cytokines and their ability to produce IL-17A and IL-17F was determined relative to healthy controls. Signal transducer and activator of transcription 3 (STAT3) phosphorylation levels were measured in stimulated neutrophil using flow cytometry. The requirement for STAT3 phosphorylation was determined by blocking its activation using a specific chemical inhibitor. RESULTS: Stimulating asthmatic neutrophils with IL-21, 23, and 6 enhanced the production of IL-17A and IL-17F at significantly higher levels comparatively to healthy controls. Stimulating neutrophils with IL-21, IL-23, and IL-6 cytokines enhanced STAT3 phosphorylation, in all cases. Interestingly, inhibiting STAT3 phosphorylation using a specific chemical inhibitor dramatically blocked the ability of neutrophils to produce IL-17, demonstrating that STAT3 activation is the major factor mediating IL-17 gene expression. CONCLUSIONS: These findings suggest that neutrophil infiltration in lungs of severe asthmatics may represent an important source of pro-inflammatory IL-17A and -F cytokines, a production enhanced by Th-17 regulatory cytokines, and thus providing a feedback mechanism that sustains inflammation. Our results suggest that STAT3 pathway could be a potential target for regulating neutrophilic inflammation during severe asthma.

Risk factors hindering asthma symptom control in Saudi children and adolescents.

BACKGROUND: Maintaining good control of asthma symptoms can help to prevent exacerbations and its associated complications. The Asthma Control Test (ACT) can rapidly assess the effectiveness of asthma management plan and therapy. The aim of this study was therefore to identify risk factors associated with uncontrolled asthma symptoms in young Saudi asthmatic children (3-17 years old). METHODS: In this cross-sectional hospital-based survey, the ACT was administered to 297 asthmatic children/adolescents, recruited at the emergency department (ED) of two major hospitals. RESULTS: Most recruited patients had intermittent (63.5%) and mild persistent (27.6%) asthma; few had moderate persistent (8.9%) and none had severe asthma. These patients visited the ED four times (3.9 ± 3.2), on average. Almost half of the patients stated that they had not received education about asthma (47%) or education about medication use (43%). Most patients (60.3%) had uncontrolled symptoms (ACT score ≤19), of whom the intermittent asthma patients had better scores than those with more severe symptoms. Children ≤6 years old, with symptoms diagnosed <5 years previously and who were not attending school, had significantly worse control than older patients. Poor medication compliance and inappropriate inhaler device use were ascribed to younger patients (<12 years old) and worse scores; particularly in relation to stopping inhaled corticosteroid therapy when their symptoms improve. Patients with poor control also stated that they had not received education about inhaler device use. CONCLUSIONS: Most Saudi asthmatic children/adolescents visiting the ED had poor control of symptoms; indeed, none achieved complete control, which is related to deficient medication compliance and improper medication inhaler device use; deficient knowledge about asthma was also another factor hindering control.

Th-17 regulatory cytokines inhibit corticosteroid induced airway structural cells apoptosis.

BACKGROUND: Although corticosteroid is a powerful anti-inflammatory drug that is used widely to control asthma, still severe asthmatics can develop steroid resistance. Airway fibroblasts are quite resistant to steroids during Idiopathic pulmonary fibrosis (IPF) and fibrosis in asthmatic lungs is not always controlled. Th-17 regulatory cytokine which are elevated in lung tissues of asthmatics were shown to enhance the survival of various types of cells. STAT factors are central to this anti-apoptotic function. However, it is not yet clear whether these cytokines contribute to steroid hypo-responsiveness in asthma. Therefore, in this study, we investigated the ability of Th-17 regulatory cytokines, specifically IL-21, IL22 and IL23, to protect structural airway cells against dexamethasone-induced apoptosis. METHODS: Primary human fibroblasts, ASM cells, and lung endothelial cells line were treated with IL-21, IL-22, and IL-23 cytokines before incubation with dexamethasone and the level of apoptosis was determined by measuring cellular Annexin-V using Flow cytometry. RESULTS: Our data indicated that treatment with Th-17 regulatory cytokines was effective in inhibiting induced apoptosis for both fibroblasts and endothelial cells but not ASM cells. STAT3 phosphorylation levels were also upregulated in fibroblasts and endothelial upon treatment with these cytokines. Interestingly, inhibiting STAT3 phosphorylation abrogated IL-21, IL-22, and IL-23 anti-apoptotic effect on fibroblasts and endothelial cells. CONCLUSIONS: This data suggest that Th-17 regulatory cytokines may play a critical role in regulating the survival of fibroblasts during asthma, IPF as well as other chronic lung inflammatory diseases leading to enhanced fibrosis. Accordingly, findings of this paper may pave the way for more extensive research on the role of these regulatory cytokines in fibrosis development in various chronic inflammatory diseases.

Rs37972 and rs37973 single-nucleotide polymorphisms in the glucocorticoid-inducible 1 gene are not associated with asthma risk in a Saudi Arabian population.

OBJECTIVE: Rs37972 and rs37973 variants in the glucocorticoid-induced transcript 1 gene have been associated with inhaled glucocorticosteroid responsiveness in asthmatics; however, some discrepancies have been also reported. This study aims to determine whether rs37972 and rs37973 SNPs are associated with asthma risk in Saudi Arabian asthmatics. METHODS: Two-hundred seventy-one diagnosed asthmatics (3-65 years old) and 387 healthy control subjects of equivalent age were recruited. DNA from peripheral blood was purified, and genotyping of rs37972 and rs37973 SNPs was performed by PCR amplification of segments of interest, followed by Sanger sequencing. RESULTS: The global frequencies of the minor (risk) alleles were 28% ("T" allele, rs37972) and 30% ("G" allele, rs37973). Yates-corrected Chi-square (χ(2)) tests revealed significant differences between asthmatic and healthy groups, in allele frequencies for rs37973 SNP only (χ(2) = 3.98, Yates' p value = 0.046). Regarding genotype frequencies, a significant difference between asthmatic and healthy groups was observed for variant rs37972 only (χ(2) = 8.19, Yates' p value = 0.016). To determine a possible association of the minor "T" and "G" alleles with asthma, both the recessive and dominant genetic models were tested. For rs37973, none of the genotypes were significantly associated with asthma. Concerning rs37972, the dominant model (C/T + T/T versus C/C) indicated a significant "protective" association with asthma, in which C/T + T/T individuals had lower odds of being asthmatics than C/C individuals (OR = 0.67; 95% CI = 0.48-0.94; p = 0.019*). CONCLUSIONS: The minor alleles "T" and "G" of rs37972 and rs37973 SNPs, respectively, were not significantly associated with increased asthma risk in asthma patients from Saudi Arabia.

Risk factors and visual results in cases of LASIK flap repositioning due to folds or dislocation: case series and literature review.

The presence of a corneal flap is a hallmark of laser in situ keratomileusis (LASIK), which offers advantages in terms of speed of visual recovery; however, it also carries the risk of postoperative flap displacement. We conducted a retrospective review of all consecutive eyes on which LASIK was performed by one single surgeon at an ophthalmological institute in Colombia between May 2005 and January 2011, looking for eyes that required flap repositioning. Demographic data, preoperative refraction, hinge position, and visual outcomes following flap repositioning were evaluated. A literature review on the subject was also conducted. We found 37 eyes on which flap repositioning was performed-12 eyes (32.4 %) with subluxation and 25 eyes (67.6 %) with folds; 21 eyes (56.8 %) had a temporal hinge and 16 eyes (43.2 %) had a superior hinge. With regard to the total number of eyes on which LASIK was performed (2,595), the overall incidence was 1.4 %. Sixteen out of 2,093 eyes (0.8 %) with a superior hinge and 21 out of 502 eyes (4.2 %) with a temporal hinge had flap-related postoperative complications (p < 0.00). A final best-corrected visual acuity (BCVA) between 20/20 and 20/25 was found in 75.7 % and a final BCVA between 20/30 and 20/40 was found in 21.6 %. Only one eye had less than 20/40 (previous amblyopia). From the eight eyes with a BCVA between 20/30 and 20/40, three had residual microstriae and one had corneal haze. Six eyes (16.2 %) lost two or more lines of BCVA. Flap subluxation or folds requiring flap repositioning were significantly more frequent when a temporal hinge was used.

Clinical History Method versus Corneal Tomographers in Estimating Corneal Power after Photorefractive Surgery

AIMS: To investigate the concordance between the corneal power determined by various approaches with two tomographers (MS-39® and Galilei G6®) and the clinical history method (CHM) in patients undergoing photorefractive surgery with excimer laser for myopic errors. MATERIAL AND METHODS: Prospective cohort study. Patients undergoing keratorefractive surgery, and having pre- and postoperative keratometries, and tomographies, were included. RESULTS: In 90 eyes, the differences in the power estimated by the CHM and the one determined by four approaches with the corneal tomographers, which included measurements of the posterior cornea, did not show statistically significant differences in their averages. However, the 95% limits of agreement were very wide. After obtaining regression formulas to adjust the values of these four variables, the results of the agreement analysis were similar. CONCLUSION: Although certain values either directly determined or derived from measurements with the Galilei® and MS-39®corneal tomographers, approximated the estimated value of postoperative corneal power according to the CHM, due to the amplitude of their limits of agreement, these calculations must be taken with care, because they may not be accurate in a given eye.

Assessing Fuchs Corneal Endothelial Dystrophy Using Artificial Intelligence-Derived Morphometric Parameters From Specular Microscopy Images.

PURPOSE: The aim of this study was to evaluate the efficacy of artificial intelligence-derived morphometric parameters in characterizing Fuchs corneal endothelial dystrophy (FECD) from specular microscopy images. METHODS: This cross-sectional study recruited patients diagnosed with FECD, who underwent ophthalmologic evaluations, including slit-lamp examinations and corneal endothelial assessments using specular microscopy. The modified Krachmer grading scale was used for clinical FECD classification. The images were processed using a convolutional neural network for segmentation and morphometric parameter estimation, including effective endothelial cell density, guttae area ratio, coefficient of variation of size, and hexagonality. A mixed-effects model was used to assess relationships between the FECD clinical classification and measured parameters. RESULTS: Of 52 patients (104 eyes) recruited, 76 eyes were analyzed because of the exclusion of 26 eyes for poor quality retroillumination photographs. The study revealed significant discrepancies between artificial intelligence-based and built-in microscope software cell density measurements (1322 ± 489 cells/mm 2 vs. 2216 ± 509 cells/mm 2 , P < 0.001). In the central region, guttae area ratio showed the strongest correlation with modified Krachmer grades (0.60, P < 0.001). In peripheral areas, only guttae area ratio in the inferior region exhibited a marginally significant positive correlation (0.29, P < 0.05). CONCLUSIONS: This study confirms the utility of CNNs for precise FECD evaluation through specular microscopy. Guttae area ratio emerges as a compelling morphometric parameter aligning closely with modified Krachmer clinical grading. These findings set the stage for future large-scale studies, with potential applications in the assessment of irreversible corneal edema risk after phacoemulsification in FECD patients, as well as in monitoring novel FECD therapies.

Glucocorticoid receptor-beta up-regulation and steroid resistance induction by IL-17 and IL-23 cytokine stimulation in peripheral mononuclear cells.

PURPOSE: Most asthmatic patients have well controlled symptoms with regular treatment, but some require much higher doses of inhaled and oral corticosteroids, or in rare cases fail to respond; these patients may present Th-17 cell infiltration and associated cytokines (IL-17A and -F) in the airways, sputum and peripheral blood. Because glucocorticoid receptor-beta (GR-beta) is associated with corticosteroid resistance, we investigated whether Th-17 associated cytokines induce steroid insensitivity in PBMCs via GR-beta up-regulation. METHODS: GR-alpha, GR-beta, GILZ and IL-6 expression were analyzed in PBMCs stimulated with IL-2/IL-4, IL-17A/IL-17F and IL-23 cytokines by quantitative RT-PCR. Dexamethasone-inhibition of PHA-induced proliferation and Dexamethasone-induced apoptosis were determined by either (3)H-thymidine or CFSE-labelled cells and by Annexin-V staining and flow cytometry. RESULTS: IL-17 and IL-23 cytokines significantly increased GR-beta expression. IL-2/IL-4 significantly decreased GR-alpha expression without affecting GR-beta. IL17, IL-23 and IL2 + 4 stimulations significantly hampered Dexamethasone-inhibition of proliferation (Dex EC(50) for: IL-17A + F = 251 nM; IL-23 = 435 nM; IL2 + 4 = 950 nM; Medium = 90 nM). IL2 + 4 and IL17A + F but not IL-23, significantly hampered Dexamethasone-induced apoptosis (1400 and 320 nM Dex, respectively). Dexamethasone's trans-activation of GILZ and trans-repression of NF-kB-driven IL-6 expression were both inhibited by IL2 + 4; IL17 + IL23 antagonized Dex trans-repression in PBMC from asthmatics. CONCLUSIONS: GR-beta up-regulation by IL-17/IL-23 cytokines is associated with induced steroid insensitivity in PBMCs, observed as diminished Dexamethasone's effects on cell proliferation, apoptosis and gene regulation. Steroid resistance induced by IL-2/IL-4 was associated with decreased GR-alpha expression. This study supports the possibility that Th-17 lymphocytes and associated cytokines play a role in the mechanism of steroid hypo-responsiveness in severe asthmatics.