Dendritic cells play no significant role in the laser-induced choroidal neovascularization model.

Age-related macular degeneration (AMD) is genetically associated with complement. Dendritic cells (DCs) play key roles during innate and adaptive immunity, and express complement components and their receptors. We investigated ocular DC heterogeneity and the role of DCs in the laser-induced choroidal neovascularization (CNV) model. In order to determine the function of DCs, we used two models of DC deficiency: the Flt3-/- and Flt3l-/- mouse. We identified three types of ocular DCs: plasmacytoid DC, classical DC-1, and classical DC-2. At steady-state, classical DCs were found in the iris and choroid but were not detectable in the retina. Plasmacytoid DCs existed at very low levels in iris, choroid, and retina. After laser injury, the number of each DC subset was up-regulated in the choroid and retina. In Flt3-/- mice, we found reduced numbers of classical DCs at steady-state, but each DC subset equally increased after laser injury between wildtype and Flt3-/- mice. In Flt3l-/- mice, each DC subsets was severely reduced after laser injury. Neither Flt3-/- or Flt3l-/- mice demonstrated reduced CNV area compared to wildtype mice. DCs do not play any significant role during the laser-induced CNV model of neovascular AMD.

Age-dependent favorable visual recovery despite significant retinal atrophy in pediatric MOGAD: how much retina do you really need to see well?

BACKGROUND: To investigate age-related severity, patterns of retinal structural damage, and functional visual recovery in pediatric and adult cohorts of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) optic neuritis (ON). METHODS: All MOGAD patients from the 5 participating centers were included. Patients with initial manifestation <18 years were included in the pediatric (MOGADped) cohort and patients with ≥18 years in the adult (MOGADadult) cohort. For patients with MOGAD ON, examinations at least ≥6 months after ON onset were included in the analyses. Using spectral domain optical coherence tomography (SD-OCT), we acquired peripapillary retinal nerve fiber layer thickness (pRNFL) and volumes of combined ganglion cell and inner plexiform layer (GCIPL). High- and 2.5% low-contrast visual acuity (HCVA, LCVA) and visual-evoked potentials (VEP) were obtained. RESULTS: Twenty MOGADped (10.3±3.7 years, 30 MOGAD ON eyes) and 39 MOGADadult (34.9±11.6 years, 42 MOGAD ON eyes) patients were included. The average number of ON episodes per ON eye was similar in both groups (1.8±1.3 and 2.0±1.7). In both pediatric and adult MOGAD, ON led to pronounced neuroaxonal retinal atrophy (pRNFL: 63.1±18.7 and 64.3±22.9 µm; GCIPL: 0.42±0.09 and 0.44±0.13 mm3, respectively) and moderate delay of the VEP latencies (117.9±10.7 and 118.0±14.5 ms). In contrast, visual acuity was substantially better in children (HCVA: 51.4±9.3 vs. 35.0±20.6 raw letters, p=0.001; LCVA: 22.8±14.6 vs. 13.5±16.4, p=0.028). Complete visual recovery (HCVA-logMAR 0.0) occurred in 73.3% of MOGADped and 31% MOGADadults ON eyes, while 3.3% and 31% demonstrated moderate to severe (logMAR > 0.5) visual impairment. Independent of retinal atrophy, age at ON onset significantly correlated with visual outcome. CONCLUSION: Pediatric MOGAD ON showed better visual recovery than adult MOGAD ON despite profound and almost identical neuroaxonal retinal atrophy. Age-related cortical neuroplasticity may account for the substantial discrepancy between structural changes and functional outcomes.

Resultados visuales en pacientes operados de queratoplastia lamelar anterior profunda versus queratoplastia penetrante en el queratocono / Visual results in patients operated of deep anterior lamellar keratoplasty versus penetrating keratoplasty in keratoconus

RESUMEN Objetivo: Comparar los resultados visuales de la queratoplastia lamelar anterior profunda versus la queratoplastia penetrante en el tratamiento quirúrgico del queratocono. Métodos: Se realizó un estudio analítico longitudinal prospectivo en 81 pacientes con queratocono, operados de queratoplastia penetrante y queratoplastia lamelar anterior profunda entre los años 2014 y 2018. Se evaluó la edad, el sexo, la agudeza visual corregida, la esfera, el cilindro y el equivalente esférico. Resultados: La media de edad en operados de queratoplastia lamelar anterior profunda fue 27,5 ± 10,0 años, y 33,2 ± 12,9 años en operados de queratoplastia penetrante. En ambos grupos predominó el sexo masculino: 62,5 por ciento en el grupo de queratoplastia lamelar anterior profunda y 63,3 por ciento en el de queratoplastia penetrante. La agudeza visual corregida poscirugía en operados de queratoplastia lamelar anterior profunda fue 0,8 ± 0,19; el cilindro refractivo -3,50 ± 1,50; el equivalente esférico -6,07 ± 3,61, SimK1 de 46,37 ± 2,47 dioptrías y SimK2, 43,05 ± 2,47 dioptrías. En la queratoplastia penetrante, la agudeza visual corregida fue 0,68 ± 0,19; el cilindro refractivo -2,77 ± 0,98 dioptrías; el equivalente esférico -3,68 ± 1,56 dioptrías, SimK1 y SimK2 de 44,58 ± 2,77 dioptrías y 41,40 ± 2,93 dioptrías respectivamente. Conclusiones: Los resultados refractivos son similares en ambas técnicas quirúrgicas(AU)

ABSTRACT Objective: Compare the visual results of deep anterior lamellar keratoplasty versus penetrating keratoplasty in the surgical treatment of keratoconus. Methods: A longitudinal analytical prospective study was carried out in 81 patients with keratoconus, operated of penetrating keratoplasty and deep anterior lamellar keratoplasty between the years 2014 and 2018. The variables analyzed were the age, the sex, the corrected visual sharpness, the sphere, the cylinder and the spherical equivalent. Results: The average of age in operated patients of deep anterior lamellar keratoplasty was 27,5 ± 10,0 years, and 33,2 ± 12,9 years in operated of penetrating keratoplasty. In both groups the masculine sex predominated: 62,5 percent in the group of deep anterior lamellar keratoplasty and 63,3 percent in penetrating keratoplasty. The corrected visual sharpness in operated of queratoplastia lamelar previous deep was 0,8 ± 0,19; the refractive cylinder -3,50 ± 1,50; the spherical equivalent -6,07 ± 3,61, SimK1 of 46,37 ± 2,47 dioptres and SimK2, 43,05 ± 2,47 dioptres. In the penetrating keratoplasty, the corrected visual sharpness was 0,68 ± 0,19; the refractive cylinder -2,77 ± 0,98 dioptres; the spherical equivalent -3,68 ± 1,56 dioptres, SimK1 and SimK2 of 44,58 ± 2,77 dioptres and 41,40 ± 2,93 dioptres respectively. Conclusions: The refractive results are similar in both surgical technicians(AU)

Comparative Effect of Feeding Human Milk as Opposed to Formula on Visual Function and Ocular Anatomy.

Background/Objective: Performance of ocular examinations on children who were breastfed, fed with formula, and combination of the two for the first 6 months of age. Subsequently, refractive errors, allergic conjunctivitis, and retinal nerve fiber layer (RNFL) thickness were evaluated. Materials and Methods: The present study included a total of 242 eyes of 121 children (aged 60-84 months, 65 males, 56 females) admitted to the outpatient clinic of our institution. The patients were divided into three groups according to their feeding pattern during their first 6 months postdelivery: breastfed children (Group 1, n = 40), children fed with a combination of breast and formula milk (Group 2, n = 41), and children exclusively fed with formula-milk (Group 3, n = 40). All patients underwent detailed ophthalmologic examinations, and measurements of the RNFLs were recorded. Results: No significant difference was observed between the groups in terms of refractive error. In Group 3, we found that allergic conjunctivitis was significantly higher than in the other groups. In addition, in Group 3, the thickness of the RNFL was found to be significantly higher in the superior quadrants of both the eyes of children than in Groups 1 and 2 (p < 0.05). Conclusions: We found that the type of feeding experienced by infants in their first 6 months has no effect on refractive error but has significant effects on both allergic conjunctivitis and RNFL. To determine the cause of this difference in the RNFL and to further validate the present study, future studies with larger patient groups and animal experiments are needed.

Safety and efficacy of autologous serum eye drop for treatment of dry eyes in graft-versus-host disease.

PURPOSE: To evaluate the treatment of autologous serum eye drops (ASED) on dry eyes in patients with graft-versus-host disease (GVHD). METHODS: A retrospective chart review of 35 patients with a history of ocular GVHD following hematopoietic stem cell transplantation that used ASED to alleviate dry eye symptoms was performed. Patients were categorized into three different groups. If patients had available ophthalmic data before and after starting treatment was group 1 (n = 14), had available ophthalmic data after starting treatment in group 2 (n = 10) and had available ophthalmic data before treatment or did not have any data after starting treatment in group 3 (n = 11). Data were collected on patient's age, gender, primary diagnosis, visual acuity and fluorescein corneal staining were collected on individual eyes in order to evaluate the efficacy of the ASED on alleviating dry eye-related signs and symptoms. RESULTS: No adverse ocular effect from the ASED was found in our series (except one fungal keratitis). All patients reported either improvement (55%) or stability (45%) in their ocular symptoms upon the use of ASED. In patients with available data before and after starting treatment, the corneal staining score improved by a median of 1 (p = 0.003) and the LogMAR visual acuity had a non-significant improvement. CONCLUSION: In our study, ASED used by patients with ocular GVHD were both safe and effective. ASED should be considered in patients with GVHD who suffer from dry eyes.

[Multicenter Prospective Observational Study of Fungal Keratitis--Current Status of Patients' Background, Clinical Findings, Treatment and Prognosis].

PURPOSE: To investigate the current status of fungal keratitis in Japan. METHODS: The patients with fungal keratitis were examined at 27 facilities in Japan from November 1st 2011 to October 31st 2013, concerning isolates, patient background, clinical findings, treatment and prognosis. RESULTS: Out of 139 cases, 133 were diagnosed as fungal keratitis, of which fungi were isolated from 72 samples of 71 cases (yeast-like fungi 32 strains and filamentous fungi 40 strains). The corrected visual acuity at the first visit of 88 cases (66.2%) was less than 20/200 and 42 cases (31.6%) were involved with deep stromal lesions, indicating high proportion of severe cases in this study. Three months later, 56 cases (42.1%) were still under treatment, and corrected visual acuity of 57 cases (42.9%) was less than 20/200. In cases with yeast-like fungi, there were significantly more cases with past history of corneal diseases, ocular surgery including keratoplasty, and eye drops' use such as steroids than those with filamentous fungi. On the other hand, there were significantly more cases of filamentous fungi, with trauma on the onset and with intervention of previously attending doctors than those with yeast-like fungi. Logistic regression analyses revealed that contact lens wearing was a significant factor of good prognosis, and yeast-like fungi as one of poor outcome compared with no fungal isolation. CONCLUSION: Although the choice of antifungal drugs has been increasing, fungal keratitis is still severe, refractory and vision-threatening disease.

Exacerbation of blast-induced ocular trauma by an immune response.

BACKGROUND: Visual prognosis after an open globe injury is typically worse than after a closed globe injury due, in part, to the immune response that ensues following open globe trauma. There is a need for an animal model of open globe injury in order to investigate mechanisms of vision loss and test potential therapeutics. METHODS: The left eyes of DBA/2 J mice were exposed to an overpressure airwave blast. This strain lacks a fully functional ocular immune privilege, so even though the blast wave does not rupture the globe, immune infiltrate and neuroinflammation occurs as it would in an open globe injury. For the first month after blast wave exposure, the gross pathology, intraocular pressure, visual function, and retinal integrity of the blast-exposed eyes were monitored. Eyes were collected at three, seven, and 28 days to study the histology of the cornea, retina, and optic nerve, and perform immunohistochemical labeling with markers of cell death, oxidative stress, and inflammation. RESULTS: The overpressure airwave caused anterior injuries including corneal edema, neovascularization, and hyphema. Immune infiltrate was detected throughout the eyes after blast wave exposure. Posterior injuries included occasional retinal detachments and epiretinal membranes, large retinal pigment epithelium vacuoles, regional photoreceptor cell death, and glial reactivity. Optic nerve degeneration was evident at 28 days post-blast wave exposure. The electroretinogram (ERG) showed an early deficit in the a wave that recovered over time. Both visual acuity and the ERG b wave showed an early decrease, then a transient improvement that was followed by further decline at 28 days post-blast wave exposure. CONCLUSIONS: Ocular blast injury in the DBA/2 J mouse recapitulates damage that is characteristic of open globe injuries with the advantage of a physically intact globe that prevents complications from infection. The injury was more severe in DBA/2 J mice than in C57Bl/6 J mice, which have an intact ocular immune privilege. Early injury to the outer retina mostly recovers over time. In contrast, inner retinal dysfunction seems to drive later vision loss.

Systemic immunotherapy delays photoreceptor cell loss and prevents vascular pathology in Royal College of Surgeons rats.

PURPOSE: Degenerative retinopathies, including retinitis pigmentosa, age-related retinal degeneration, autoimmune retinopathy, and related diseases affect millions of people around the world. Currently, there is no effective treatment for most of those diseases. We investigated systemic recombinant T-cell receptor ligand (RTL) immunotherapy for preventing retinal degeneration and vascular damage in the Royal College of Surgeons (RCS) rat model of retinal degeneration. METHODS: RCS rats were treated with RTL220 tethered to interphotoreceptor retinoid binding protein (IRBP) peptide or control RTL101 without peptide by subcutaneous administration starting at the onset of photoreceptor degeneration or after the degenerative process began daily or every other day and performed for a 13-week period. The retinal cross sections and whole mounts were prepared to determine histopathology, leaking vessels, and formation of vascular complexes. Immunofluorescent studies evaluated microglia and monocyte chemoattractant protein-1 chemokine in treated retinas. Optokinetic studies were performed to determine visual acuity. RESULTS: Systemic treatment with RTL220 prevented decreases in outer nuclear layer (ONL) thickness and showed a significantly higher number of nuclei than control rats treated with RTL101 or vehicle. RTL220 was also effective in protecting retinal vasculature from leakage and the formation of abnormal vascular complexes even when the treatment was administered after the degenerative process was initiated. Visual acuity measurement showed that rats treated with RTL220 performed significantly better than those with RTL101 and untreated age-matched controls at P60 and P90. Biodistribution studies showed that RTL220 cleared slowly from the administration site. Moreover, RTL220-treated retinas had a significantly reduced number of activated microglia in the subretinal space, decreased monocyte chemoattractant protein-1 production in the retina, inhibited T-cell responses, and reduced anti-interphotoreceptor retinoid binding protein autoantibody titers. Treatment with the control RTL101 (without a specific peptide tethered) or vehicle alone did not inhibit microglia activation or protect photoreceptors or vasculature. CONCLUSIONS: RTL therapy augmented photoreceptor cell survival, protected vasculature, and increased visual function in the RTL rat. Targeting chronic autoimmunity with RTLs can be an effective therapeutic alternative in delaying retinal degeneration. Subcutaneous delivery of RTLs alone or combined with other drugs could be an attractive option for long-term therapy for retinal degenerative diseases.

Improvement of visual acuity in patients with severe visual loss affected by multiple sclerosis treated with natalizumab: a case report.

Multiple sclerosis is an important chronic disorders of central nervous system that can lead to severe disability because of the presence of multiple demyelinating lesion. We report a 20-year-old woman with relapsing-remitting MS, with pediatric onset of MS, who developed aggressive disease with visual acuity lost (1/60 in both eyes). Frequent magnetic resonance imaging (MRI) detected persisting inflammatory activity and increase of lesion burden so she was submitted to natalizumab treatment with stability of MRI. After about 10 administrations of natalizumab, she improved her visual acuity in left eye (visual acuity 1/10); visual evocate potential show mild improvement of latency in left eye.

Long-term follow-up of oral tolerance induction with HLA-peptide B27PD in patients with uveitis.

Oral tolerance induction with peptide B27PD had an ameliorating effect in uveitis patients, which was also observed in the five-year follow-up period. Repeated treatments with peptide B27PD were also effective. Side effects did not occur in this patient group, not even in patients receiving peptide for up to 42 weeks.

Patients with Multiple Sclerosis and concomitant uveitis/periphlebitis retinae are not distinct from those without intraocular inflammation.

Recent models of experimental autoimmune encephalomyelitis (EAE) have indicated that antigens co-expressed in the retina and uvea might be of pathogenetic relevance in Multiple Sclerosis (MS). We investigated the clinical spectrum and magnetic resonance imaging of 11 MS patients with concomitant uveitis, and determined the frequency of clinically silent intraocular inflammation in a prospective series of 50 patients. Two of the 11 patients had panuveitis, seven had anterior, and the remaining two had intermediate uveitis. The onset of uveitis preceded that of neurological symptoms by a mean of 8.5 years (range 1-20). None of the 50 MS patients studied prospectively by using slit lamp examinations and dilated funduscopy showed any evidence of uveitis but six patients had signs of retinal inflammation ("periphlebitis retinae"). Cranial MRI did not reveal "atypical" lesional distribution in MS patients with uveitis or periphlebitis retinae. No correlation between the type of MS and uveitis, or between the degree of neurological disability and the type of uveitis was found.

[Retinal vasculopathy associated with Berger's IgA nephropathy]. / Retinale Vaskulopathie assoziiert mit Bergers IgA-Nephropathie.

AIM: Ophthalmological complications associated with Berger's IgA nephropathy comprise scleritis, episcleritis, keratoconjunctivitis as well as anterior uveitis. We present a new association of IgA nephropathy with a retinal vasculopathy. METHODS: Presentation of two clinical cases. RESULTS: Two patients presented with hematuria and epistaxis associated with a retinal vasculopathy characterised by teleangiectasies, capillary occlusion with retinal hemorrhages, neovascularisations and macular edema with decreased visual acuity. Fluorescein angiography showed zones of non-perfusion as well as vasculitic changes. A general medical exam revealed a normal arterial pressure but a slightly elevated creatinine. Immunological investigations for the presence of antibodies showed no positive results. Renal biopsy demonstrated mesangial proliferations with diffuse deposits of IgA. Over the course of a 2 year follow-up some of the retinal changes regressed under treatment with cortisone and visual acuity returned to normal. The teleangiectasies showed no progression. CONCLUSION: Berger's IgA nephropathy can be associated with a retinal vasculopathy which may be due to local deposition of IgA immune complexes in the retinal vessels.