Minimal detectable change of the disc-fovea angle for ocular torsion assessment.

PURPOSE: The disc-fovea angle (DFA) is used as a relevant indicator of ocular torsion change in cyclovertical strabismus. However, interpretation of the variation in time must differentiate whether a real change has occurred or if the disparity is due to random measurement error. The aim of the study was to obtain the minimal detectable change (MDC) of the DFA. It represents the minimal variation between two measurements that may be considered a real ocular torsion change. METHODS: A prospective cross-sectional study was conducted in San Carlos Clinical Hospital of Madrid, Spain. Sixty healthy right eyes from 60 patients (31 men and 29 women) were recruited. Three digital fundus photographs were obtained, and between measurements, the patient moved their head away from the head support and then returned. Two observers quantified the DFA with software designed with MATLAB. Test-retest and interrater reliability were calculated. RESULTS: Mean participant age was 56.1 years (SD 16.6, range 25-85). Mean DFA was 8.1° (SD 3.5, range 1.3-18.5). Test-retest reliability for Observer 1 (Ob1), Observer 2 (Ob2) and interrater reliability were excellent (ICC 0.80, 0.83 and 0.95, respectively). Precision was 2.9° (Ob1) and 3.0° (Ob2), and the MDC95 was 4.1° (Ob1) and 4.2° (Ob2). Bland-Altman analysis revealed an absence of bias and a homoscedastic distribution of the differences. CONCLUSIONS: The MDC of the DFA in fundus photography was 4°, which represents the minimal change that may be considered a real change in ocular torsion. This result may improve the interpretation of ocular torsion changes in surgery and clinical scenarios.

Binocular Visual Field and Vision-Related Quality of Life in Patients With Hemianopia.

BACKGROUND: Hemianopias can have a severe impact on functional ability and quality of life (QoL). Binocular visual field (VF) analysis is clinically more relevant to visual function than monocular VF. The aim is to analyze the binocular VF of patients with hemianopias and its association with the monocular VF and to assess the QoL of these patients through questionnaires specifically related to vision compared with healthy controls. METHODS: The case-control study included patients with hemianopias and controls. Sex, age, general history, etiology, location of the lesion, and time since the lesion appeared were recorded. Monocular VF and Esterman binocular VF were performed. VF defect, mean defect (MD), and Esterman scores were recorded. Visual Activities Questionnaire (VAQ-33) and Visual Function Questionnaire (VFQ-25) questionnaires were administered. RESULTS: Twenty patients with hemianopia and 22 healthy controls were included. The Esterman score in homonymous hemianopia patients (n = 17) correlated with best eye MD (r = -0.62, P = 0.01), worst eye MD (r = -0.70, P = 0.002), and average MD (r = -0.68, P = 0.003). Compared with healthy control subjects, patients with homonymous hemianopia had significantly lower VFQ-25 score and in 10/12 subscales (all P < 0.001). VAQ-33 scores revealed lower overall and subscales scores with the exception of light/dark adaptation (P = 0.08). Correlations were found between monocular and binocular VF scores and general vision (r = -0.55), peripheral vision (on both questionnaires, r-range -0.75 to 0.47), VFQ-25 and VAQ-33 overall scores (r = -0.59, -0.49 and 0.50), and glare disability (r = 0.53 and 0.67). CONCLUSIONS: Hemianopic VF defects involve a major alteration in the patients' vision-related QoL.

Lifestyle Factors in Myopic Spanish Children.

BACKGROUND: Childhood myopia represents a global concern with increasing prevalence in recent decades. Lifestyle factors significantly impact myopia. AIM: To evaluate lifestyle factors in myopic children from a metropolitan area in Europe. METHODS: This was a descriptive study including myopic subjects aged 4-18 years. Patient demographic and clinical data were collected, including cycloplegic refraction in spherical equivalent refraction (SER) and axial length (AL). In addition, a questionnaire on lifestyle factors was conducted between September 2022 and April 2023. RESULTS: A total of 321 myopic children were included, aged 10.72 ± 3.05 years, of whom 51.4% were boys, with SER -2.25 ± 1.9 D and AL 24.54 ± 0.98 mm. The mean age of myopia onset was 7.69 ± 3.05 years. A total of 59.8% had family history of myopia. Those children who had <2 h/day of screen time (on weekdays) presented SER -2 ± 1.91 D, compared to those who had >2 h/day, SER: -2.50 ±1.88 D (p = 0.009). Children who spent <2 h/day doing near work after school were less myopic compared to those who spent >2 h/day (SER: -1.75 ± 1.83 vs. SER: -2.75 ± 1.82, respectively, p = 0.03). However, no significant association was observed between SER and AL and time spent outdoors nor between SER and AL and academic performance (p > 0.05). CONCLUSIONS: Screen time and near-work time appear to be lifestyle factors related to myopia.

Dendritic cells in energy balance regulation.

Besides their well-known role in initiating adaptive immune responses, several groups have studied the role of dendritic cells (DCs) in the context of chronic metabolic inflammation, such as in diet-induced obesity (DIO) or metabolic-associated fatty liver disease. DCs also have an important function in maintaining metabolic tissue homeostasis in steady-state conditions. In this review, we will briefly describe the different DC subsets, the murine models available to assess their function, and discuss the role of DCs in regulating energy balance and maintaining tissue homeostasis.

Immune synapse formation promotes lipid peroxidation and MHC-I upregulation in licensed dendritic cells for efficient priming of CD8+ T cells.

Antigen cognate dendritic cell (DC)-T cell synaptic interactions drive activation of T cells and instruct DCs. Upon receiving CD4+ T cell help, post-synaptic DCs (psDCs) are licensed to generate CD8+ T cell responses. However, the cellular and molecular mechanisms that enable psDCs licensing remain unclear. Here, we describe that antigen presentation induces an upregulation of MHC-I protein molecules and increased lipid peroxidation on psDCs in vitro and in vivo. We also show that these events mediate DC licensing. In addition, psDC adoptive transfer enhances pathogen-specific CD8+ T responses and protects mice from infection in a CD8+ T cell-dependent manner. Conversely, depletion of psDCs in vivo abrogates antigen-specific CD8+ T cell responses during immunization. Together, our data show that psDCs enable CD8+ T cell responses in vivo during vaccination and reveal crucial molecular events underlying psDC licensing.

A comparative multicentric long-term study of un-augmented modified Nishida procedure vs augmentation in unilateral sixth nerve palsy.

PURPOSE: To compare the effectiveness of three procedures: modified Nishida procedure alone vs modified Nishida procedure combined with medial rectus recession (MRc) vs modified Nishida procedure combined with MRc and botulinum toxin (BT) for severe unilateral sixth nerve palsy. DESIGN: Consecutive, interventional case series. METHODS: The medical records of a consecutive series of patients with severe unilateral sixth nerve palsy who underwent modified Nishida procedure in multiple centres were reviewed. Surgical technique was decided preoperatively at the surgeon's discretion. The preoperative and postoperative findings were compared. RESULTS: Of the 43 patients with abducens palsy that received the procedure, 32 were included (mean age 38.6 ± 19.8 years). Mean preoperative deviation was 63.0 ± 27.3 prism dioptres (PD) and mean limitation of abduction -4.5 ± 1.2. Five patients underwent a modified Nishida procedure alone, 24 patients had an additional MRc and 3 patients were also injected with BT. Overall, the average correction of modified Nishida technique by itself was 29.4 ± 6.6 PD (range 20-36) and adding a MRc corrected 62.6 ± 23.8 PD (range 24-120). Modified Nishida procedure, MRc and BT altogether corrected 95.0 ± 18.0 PD (range 75-110). No postoperative complications were observed in any of the patients. CONCLUSIONS: Excellent outcomes with fewer complications are obtained with modified Nishida procedure alone. The need for additional procedures such as MRc and BT which increase the effect in primary position can be determined depending on passive duction and preoperative horizontal deviation.

Bilaterally recurrent benign abducens nerve palsy in a child.

Benign abducens nerve palsy with recurrent episodes in children is rare. In most cases, there are two episodes, the same eye is affected, and recovery is spontaneous. We present a patient with multiple episodes in both eyes, including bilateral simultaneous involvement, who was treated with botulinum toxin.

Inferior oblique recession associated to partial temporal inferior rectus recession in unilateral congenital superior oblique palsy.

PURPOSE: To evaluate the effectiveness of inferior oblique recession with contralateral partial temporal inferior rectus recession in patients with decompensated congenital unilateral superior oblique palsy (SOP) in correcting moderate vertical deviations in primary position. METHODS: The medical records of patients with SOP who underwent inferior oblique recession with contralateral partial temporal inferior rectus recession were reviewed retrospectively. Vertical deviation in primary position, subjective torsion, diplopia, residual deviation, and the deviation decrease were evaluated. RESULTS: Four patients (three males and one female, age range 29-56 years) with congenital unilateral SOP and mean vertical deviation of 21.0 ± 5.3PD (range 14-25D) in primary position were included. Mean correction of hypertropia in primary position with this technique was 15.5 ± 5.3PD (range 10-20PD). The mean hypertropia on gaze to the contralateral side changed from 30.0 ± 10.8D before surgery to 9.3 ± 7.9D after surgery. Torsion had a mean change of 4.8° of incyclodeviation. Preoperatively, all patients had head tilt and diplopia, which was resolved in all but one patient, who will need surgery. Patients were followed an average of 18 months. No adverse events were reported in any subjects. CONCLUSION: When performing recession of inferior oblique muscles in SOP associated to a full recession of the contralateral inferior rectus, there is a risk of overcorrection in those with moderate angles. Performing a partial recession in the contralateral inferior rectus eye corrected up to 20PD in primary position in our series, reducing this risk.

Abducens and Trochlear Nerve Palsies After COVID-19 Vaccination: Report of Two Cases.

The authors report two cases of an abducens palsy and a trochlear nerve palsy, respectively, in two patients who received a coronavirus disease 2019 (COVID-19) vaccine 2 weeks previously. Given the lack of other symptoms, normal test results, and spontaneous resolution of the diplopia, a likely association with the COVID-19 vaccine was suggested. [J Pediatr Ophthalmol Strabismus. 2022;59(5):e50-e53.].

Blue Cone Monochromatism: A Case Report with Opsoclonus and Light Exposure.

Blue cone monochromatism (BCM) is a rare X-linked congenital vision disorder that is characterized by a cone dysfunction. We present a case of a 3-year-old boy referred to our department with abnormal eye movements since birth, impaired vision, and difficulties in distinguishing colors. A tendency to stare at the sun was noted. Examination revealed severe loss of visual acuity, high myopia, and opsoclonus. A mutation screening of OPN1LW / OPN1MW gene cluster was performed showing a nucleotide substitution encoding a Cys203Arg (C203R) missense mutation. The diagnosis of BCM in this case was clear and the patient harbored the most frequent genetic alteration. Opsoclonus and continued voluntary light exposure are novel features that have not been previously reported in BCM.

Conventional type 1 dendritic cells protect against age-related adipose tissue dysfunction and obesity.

Conventional dendritic cells (cDCs) scan and integrate environmental cues in almost every tissue, including exogenous metabolic signals. While cDCs are critical in maintaining immune balance, their role in preserving energy homeostasis is unclear. Here, we showed that Batf3-deficient mice lacking conventional type 1 DCs (cDC1s) had increased body weight and adiposity during aging. This led to impaired energy expenditure and glucose tolerance, insulin resistance, dyslipidemia, and liver steatosis. cDC1 deficiency caused adipose tissue inflammation that was preceded by a paucity of NK1.1+ invariant NKT (iNKT) cells. Accordingly, among antigen-presenting cells, cDC1s exhibited notable induction of IFN-γ production by iNKT cells, which plays a metabolically protective role in lean adipose tissue. Flt3L treatment, which expands the dendritic cell (DC) compartment, mitigated diet-induced obesity and hyperlipidemia in a Batf3-dependent manner. This effect was partially mediated by NK1.1+ cells. These results reveal a new critical role for the cDC1-iNKT cell axis in the regulation of adipose tissue homeostasis.

Inoculation of the Leishmania infantum HSP70-II Null Mutant Induces Long-Term Protection against L. amazonensis Infection in BALB/c Mice.

Leishmania amazonensis parasites are etiological agents of cutaneous leishmaniasis in the New World. BALB/c mice are highly susceptible to L. amazonensis challenge due to their inability to mount parasite-dependent IFN-γ-mediated responses. Here, we analyzed the capacity of a single administration of the LiΔHSP70-II genetically-modified attenuated L. infantum line in preventing cutaneous leishmaniasis in mice challenged with L. amazonensis virulent parasites. In previous studies, this live attenuated vaccine has demonstrated to induce long-protection against murine leishmaniasis due to Old World Leishmania species. Vaccinated mice showed a reduction in the disease evolution due to L. amazonensis challenge, namely reduction in cutaneous lesions and parasite burdens. In contrast to control animals, after the challenge, protected mice showed anti-Leishmania IgG2a circulating antibodies accompanied to the induction of Leishmania-driven specific IFN-γ systemic response. An analysis performed in the lymph node draining the site of infection revealed an increase of the parasite-specific IFN-ϒ production by CD4+ and CD8+ T cells and a decrease in the secretion of IL-10 against leishmanial antigens. Since the immunity caused by the inoculation of this live vaccine generates protection against different forms of murine leishmaniasis, we postulate LiΔHSP70-II as a candidate for the development of human vaccines.

DNGR-1 limits Flt3L-mediated antitumor immunity by restraining tumor-infiltrating type I conventional dendritic cells.

BACKGROUND: Conventional type 1 dendritic cells (cDC1s) are central to antitumor immunity and their presence in the tumor microenvironment associates with improved outcomes in patients with cancer. DNGR-1 (CLEC9A) is a dead cell-sensing receptor highly restricted to cDC1s. DNGR-1 has been involved in both cross-presentation of dead cell-associated antigens and processes of disease tolerance, but its role in antitumor immunity has not been clarified yet. METHODS: B16 and MC38 tumor cell lines were inoculated subcutaneously into wild-type (WT) and DNGR-1-deficient mice. To overexpress Flt3L systemically, we performed gene therapy through the hydrodynamic injection of an Flt3L-encoding plasmid. To characterize the immune response, we performed flow cytometry and RNA-Seq of tumor-infiltrating cDC1s. RESULTS: Here, we found that cross-presentation of tumor antigens in the steady state was DNGR-1-independent. However, on Flt3L systemic overexpression, tumor growth was delayed in DNGR-1-deficient mice compared with WT mice. Of note, this protection was recapitulated by anti-DNGR-1-blocking antibodies in mice following Flt3L gene therapy. This improved antitumor immunity was associated with Batf3-dependent enhanced accumulation of CD8+ T cells and cDC1s within tumors. Mechanistically, the deficiency in DNGR-1 boosted an Flt3L-induced specific inflammatory gene signature in cDC1s, including Ccl5 expression. Indeed, the increased infiltration of cDC1s within tumors and their protective effect rely on CCL5/CCR5 chemoattraction. Moreover, FLT3LG and CCL5 or CCR5 gene expression signatures correlate with an enhanced cDC1 signature and a favorable overall survival in patients with cancer. Notably, cyclophosphamide elevated serum Flt3L levels and, in combination with the absence of DNGR-1, synergized against tumor growth. CONCLUSION: DNGR-1 limits the accumulation of tumor-infiltrating cDC1s promoted by Flt3L. Thus, DNGR-1 blockade may improve antitumor immunity in tumor therapy settings associated to high Flt3L expression.

SHP-1 Regulates Antigen Cross-Presentation and Is Exploited by Leishmania to Evade Immunity.

Intracellular pathogens have evolved strategies to evade detection by cytotoxic CD8+ T lymphocytes (CTLs). Here, we ask whether Leishmania parasites trigger the SHP-1-FcRγ chain inhibitory axis to dampen antigen cross-presentation in dendritic cells expressing the C-type lectin receptor Mincle. We find increased cross-priming of CTLs in Leishmania-infected mice deficient for Mincle or with a selective loss of SHP-1 in CD11c+ cells. The latter also shows improved cross-presentation of cell-associated viral antigens. CTL activation in vitro reveals increased MHC class I-peptide complex expression in Mincle- or SHP-1-deficient CD11c+ cells. Neuraminidase treatment also boosts cross-presentation, suggesting that Leishmania triggers SHP-1-associated sialic-acid-binding receptors. Mechanistically, enhanced antigen processing correlates with reduced endosomal acidification in the absence of SHP-1. Finally, we demonstrate that SHP-1 inhibition improves CD11c+ cell-based vaccination against the parasite. Thus, SHP-1-mediated impairment of cross-presentation can be exploited by pathogens to evade CTLs, and SHP-1 inhibition improves CTL responses during vaccination.

Resistance to Experimental Visceral Leishmaniasis in Mice Infected With Leishmania infantum Requires Batf3.

Unveiling the protective immune response to visceral leishmaniasis is critical for a rational design of vaccines aimed at reducing the impact caused by this fatal, if left untreated, vector-borne disease. In this study we sought to determine the role of the basic leucine zipper transcription factor ATF-like 3 (Batf3) in the evolution of infection with Leishmania infantum, the causative agent of human visceral leishmaniasis in the Mediterranean Basin and Latin America. For that, Batf3-deficient mice in C57BL/6 background were infected with an L. infantum strain expressing the luciferase gene. Bioluminescent imaging, as well as in vitro parasite titration, demonstrated that Batf3-deficient mice were unable to control hepatic parasitosis as opposed to wild-type C57BL/6 mice. The impaired microbicide capacities of L. infantum-infected macrophages from Batf3-deficient mice mainly correlated with a reduction of parasite-specific IFN-γ production. Our results reinforce the implication of Batf3 in the generation of type 1 immunity against infectious diseases.

Subcutaneous Immunization of Leishmania HSP70-II Null Mutant Line Reduces the Severity of the Experimental Visceral Leishmaniasis in BALB/c Mice.

Leishmania infantum parasites cause a severe form of visceral leishmaniasis in human and viscerocutaneous leishmaniasis in dogs. Recently, we reported that immunization with an attenuated L. infantum cell line, lacking the hsp70-II gene, protects against the development of murine cutaneous leishmaniasis. In this work, we analyzed the vaccine potential of this cell line towards the long-term protection against murine visceral leishmaniasis. This model shows an organ-dependent evolution of the disease. The infection can resolve in the liver but chronically affect spleen and bone marrow. Twelve weeks after subcutaneous administration of attenuated L. infantum, Bagg Albino (BALB/c) mice were challenged with infective L. infantum parasites expressing the luciferase-encoding gene. Combining in vivo bioimaging techniques with limiting dilution experiments, we report that, in the initial phase of the disease, vaccinated animals presented lower parasite loads than unvaccinated animals. A reduction of the severity of liver damage was also detected. Protection was associated with the induction of rapid parasite-specific IFN-γ production by CD4+ and CD8+ T cells. However, the vaccine was unable to control the chronic phase of the disease, since we did not find differences in the parasite burdens nor in the immune response at that time point.

Plasma Cell-Rich Acute Rejection in Renal Transplantation: A Case Report.

Plasma cell-rich acute rejection (PCAR) is a rare type of allograft rejection in renal transplantation. It is characterized by the presence of mature plasma cells that compromise more than 10% of inflammatory cells infiltrating the renal graft. The pathogenesis of PCAR is unknown, appears late, and has been related mainly to insufficient immunosuppression or infections. The treatment is not clearly defined, and the graft survival is poor. Here, we report a case series of 3 Spanish patients diagnosed with PCAR accompanied by donor-specific antibodies (DSA) after kidney transplantation. Mean to diagnosis was 2-12 years post-transplantation, and they began with abrupt deterioration of renal function. All patients were women and had preceding viral infection. In addition, two of the three patients recognize a doubtful adherence to immunosuppression. About treatment, 2 of the 3 patients, because the biopsy of the renal graft showed signs suggestive of incipient antibody-mediated rejection (ABMR) (glomerulitis, capilaritis, transplant glomerulopathy), were started with corticosteroids, anti-thymoglobulin, plasmapheresis, and intravenous immunoglobulins. The last patient, who only showed PCAR at biopsy, was treated with corticosteroids and anti-thymoglobulin. After treatment, graft function improved in all of them, but one patient developed an ABMR and another required a dialysis program, all of which indicates the difficulty in management and treatment of PCAR.