Childhood-Onset Non-Infectious Uveitis in the "Biologic Era". Results From Spanish Multicenter Multidisciplinary Real-World Clinical Settings.

OBJECTIVE: To characterize and describe clinical experience with childhood-onset non-infectious uveitis. STUDY DESIGN: A multicenter retrospective multidisciplinary national web-based registry of 507 patients from 21 hospitals was analyzed. Cases were grouped as immune disease-associated (IMDu), idiopathic (IDIu) or ophthalmologically distinct. Characteristics of juvenile idiopathic arthritis-associated (non-HLA-B27-related) uveitis (JIAu), IDIu, and pars planitis (PP) were compared. RESULTS: IMDu (62.3%) and JIAu (51.9%) predominated in young females; and IDIu (22.7%) and PP (13.6%) in older children, without sex imbalance. Ocular complications occurred in 45.3% of cases (posterior synechiae [28%], cataracts [16%], band keratopathy [14%], ocular hypertension [11%] and cystoid macular edema [10%]) and were associated with synthetic (86%) and biologic (65%) disease-modifying antirheumatic drug (DMARD) use. Subgroups were significantly associated (p < 0.05) with different characteristics. JIAu was typically anterior (98%), insidious (75%), in ANA-positive (69%), young females (82%) with fewer complications (31%), better visual outcomes, and later use of uveitis-effective biologics. In contrast, IDIu was characteristically anterior (87%) or panuveitic (12.1%), with acute onset (60%) and more complications at onset (59%: synechiae [31%] and cataracts [9.6%]) and less DMARD use, while PP is intermediate, and was mostly bilateral (72.5%), persistent (86.5%) and chronic (86.8%), with more complications (70%; mainly posterior segment and cataracts at last visit), impaired visual acuity at onset, and greater systemic (81.2%), subtenon (29.1%) and intravitreal (10.1%) steroid use. CONCLUSION: Prognosis of childhood uveitis has improved in the "biologic era," particularly in JIAu. Early referral and DMARD therapy may reduce steroid use and improve outcomes, especially in PP and IDIu.

Effects of Type 2 Diabetes on the Neuropsychological Profile in Mild Cognitive Impairment.

Background: Diabetes is one of the main risk factors for developing mild cognitive impairment (MCI) and Alzheimer's disease. Most studies have demonstrated a worse performance in executive function, verbal fluency, and information processing speed in patients with diabetes. Objective: To assess the cognitive functioning of persons with type 2 diabetes and amnesic mild cognitive impairment (aMCI-T2DM) compared to persons with aMCI without diabetes and persons without diabetes or aMCI as controls, to understand the role of diabetes in the neuropsychological profile. Methods: Cross-sectional study involving a sample of 83 patients, ranging in age from 61 to 85 years and divided into three groups: aMCI-T2DM (27 patients), aMCI (29 patients), Controls (27 individuals). All the participants undertook an exhaustive neuropsychological assessment (auditory-verbal and visual memory, attention, information processing speed, language, executive function, and depression). Results: Both groups of aMCI patients performed significantly worse than the controls in all the neuropsychological tests. A significant linear tendency (p trend <  0.05) was found between groups, with the aMCI-T2DM group presenting worse results in global cognition assessed by the Mini-Mental State Examination and Montreal Cognitive Assessment; Rey-Osterrieth Complex Figure Test; Auditory Verbal Learning Test; Trail Making Test A and B, Verbal Fluency Test, and Hamilton Depression Rating Scale. Conclusions: aMCI patients with or without diabetes showed worse cognitive function compared to persons without diabetes or aMCI. Additionally, aMCI patients without T2DM presented a different cognitive profile than aMCI patients with T2DM, which tended towards presenting worse cognitive functions such as global cognition, memory, attention, executive function, and language.

Treatment of orbital lymphatic malformation with oral sirolimus: a case report / Malformação linfática orbital tratada com sirolimo oral: relato de caso

ABSTRACT It is estimated that lymphatic malformations in children account for 6% of all benign vascular malformations. New medical therapies have been developed for the management of lymphatic orbital disease. The purpose of this article was to describe a clinical case of orbital venolymphatic malformation in a 10-year-old boy, causing proptosis and palpebral edema. The lesion was initially treated with local sclerotherapy. However, the lesion relapsed, and was successfully treated with oral sirolimus. Prospective studies are warranted to determine the appropriate dose and extend the indications of sirolimus in these patients.

RESUMO A incidência de malformações linfáticas em crianças é estimada em 6% de todas as malformações vasculares benignas. Têm sido desenvolvidos novos tratamento para doenças linfáticas orbitárias. Nosso objetivo é descrever um caso clínico de malformação venolinfática orbitária em um menino de 10 anos de idade, causando proptose e edema palpebral. A lesão foi tratada inicialmente com escleroterapia local. No entanto, a lesão teve recidiva e foi tratada com sucesso com sirolimo oral. Ainda são necessários estudos prospectivos para estabelecer a dose apropriada e a duração do tratamento com sirolimo nesses pacientes.

Structural and Functional Retinal Changes in Patients with Mild Cognitive Impairment with and without Diabetes.

Our objective is to analyze retinal changes using optical coherence tomography angiography (OCT-A) in patients with mild cognitive impairment (MCI) to characterize structural and vascular alterations. This cross-sectional study involved 117 eyes: 39 eyes from patients with MCI plus diabetes (DM-MCI), 39 eyes from patients with MCI but no diabetes (MCI); and 39 healthy control eyes (C). All patients underwent a visual acuity measurement, a structural OCT, an OCT-A, and a neuropsychological examination. Our study showed a thinning of retinal nerve fiber layer thickness (RNFL) and a decrease in macular thickness when comparing the MCI-DM group to the C group (p = 0.008 and p = 0.016, respectively). In addition, an increase in arteriolar thickness (p = 0.016), a reduction in superficial capillary plexus density (p = 0.002), and a decrease in ganglion cell thickness (p = 0.027) were found when comparing the MCI-DM group with the MCI group. Diabetes may exacerbate retinal vascular changes when combined with mild cognitive impairment.

Allergen exposure boosts peripheral Th9 responses in patients with local allergic rhinitis.

KEY POINTS: Intranasal allergen exposure increases peripheral total Th2 and Th9 cells in patients with local allergic rhinitis (LAR). Peripheral T-cell response seems dominated by Th9 cells in patients with LAR, whereas Th2 responses prevail in patients with allergic rhinitis. Our results identify Th9 cells as potential therapeutic targets for patients with LAR.

Retinal Neurodegeneration Measured With Optical Coherence Tomography and Neuroimaging in Alzheimer Disease: A Systematic Review.

BACKGROUND: Optical coherence tomography (OCT) has enabled several retinal alterations to be detected in patients with Alzheimer disease (AD), alterations that could be potential biomarkers. However, the relationship between the retina and other biomarkers of AD has been underresearched. We gathered and analyzed the literature about the relationship between retinal and cerebral alterations detected via neuroimaging in patients with AD, mild cognitive impairment (MCI), and preclinical AD. METHODS: This systematic review followed the PRISMA Statement guidelines through the 27 items on its checklist. We searched in PubMed, BVS, Scopus, and the Cochrane Library, using the keywords: Alzheimer's disease, optical coherence tomography, white matter, cortex, atrophy, cortical thickness, neuroimaging, magnetic resonance imaging, and positron emission tomography. We included articles that studied the retina in relation to neuroimaging in patients with AD, MCI, and preclinical AD. We excluded studies without OCT, without neuroimaging, clinical cases, opinion articles, systematic reviews, and animal studies. RESULTS: Of a total of 35 articles found, 23 were finally included. Although mixed results were found, most of these corroborate the relationship between retinal and brain disorders. CONCLUSIONS: More rigorous research is needed in the field, including homogenized, longitudinal, and prolonged follow-up studies, as well as studies that include all stages of AD. This will enable better understanding of the retina and its implications in AD, leading to the discovery of retinal biomarkers that reflect brain alterations in AD patients in an accessible and noninvasive manner.

MULTI-MODAL IMAGING IN DIFFUSE SUBRETINAL FIBROSIS WITH UVEITIS SYNDROME.

PURPOSE: To describe clinical features including multimodal imaging in a case of diffuse subretinal fibrosis and uveitis syndrome. METHODS: A young patient presented with counting fingers in both eyes due to posterior uveitis and unresponsive to systemic corticosteroids. Ultra-wide field pseudo-color and autofluorescence imaging, optical coherence tomography angiography (OCT-A), en-face OCT-A, and spectral-domain optical coherence were performed. RESULTS: Clinical examination revealed a bilateral fibrosis plaque in both fovea and macular multifocal choroidal lesions associated, with no vitritis. Ultra-wide field-autofluorescence allowed us to determine activity showing a hyperfluorescent pattern. En-face OCT-A at the level of the ellipsoid layer showed multiple hyperreflective lesions surrounding a hyperreflective fibrosis plaque in both eyes, which improved and stabilized during the follow-up. Optical coherence tomography angiography at the level of retina pigmentary epithelium-choriocapillaris revealed neocapillary network changes along the chronification of the disease. The patient required the addition of intravitreal dexamethasone implants (Ozurdex) to control the acute rebounds and anti-TNFα to control the underlying inflammatory process. CONCLUSION: This is the first diffuse subretinal fibrosis with uveitis syndrome reported with a complete En-face OCT-A and OCT-A examination. This multi-modal imaging will improve the monitoring of the disease's activity and the chronicity changes.

Treatment of orbital lymphatic malformation with oral sirolimus: a case report.

It is estimated that lymphatic malformations in children account for 6% of all benign vascular malformations. New medical therapies have been developed for the management of lymphatic orbital disease. The purpose of this article was to describe a clinical case of orbital venolymphatic malformation in a 10-year-old boy, causing proptosis and palpebral edema. The lesion was initially treated with local sclerotherapy. However, the lesion relapsed, and was successfully treated with oral sirolimus. Prospective studies are warranted to determine the appropriate dose and extend the indications of sirolimus in these patients.

Autologous versus allogeneic versus umbilical cord sera for the treatment of severe dry eye disease: a double-blind randomized clinical trial.

PURPOSE: To measure the effects of Autologous serum (AS), Allogeneic Serum (HS) and Umbilical Cord serum (CS) eye drops in severe dry eye disease (DES), as well as to characterize and quantify several molecules in the three sera (albumin, fibronectin; Vitamin A and E; IgG, IgA and IgM; Transforming growth factor ß; Epithelial growth factor). METHODS: Randomized, double-blind, single-centre, three-arm (AS, HS and CS) clinical trial. Sixty-three subjects were included with severe DES, 21 in each arm of the study. Visual acuity, Schirmer test, Breakup time (BUT), lissamine green, fluorescein staining measurements and a questionnaire were performed prior to treatment, and after one-month and three-month follow-up. RESULTS: There was a significant main effect of time on visual acuities, Schirmer and BUT tests and fluorescein and lissamine green staining measurements and questionnaire scores (p = 0.015, p = 0.002, p < 0.001, p < 0.001, p = 0.031 and p < 0.001, respectively), although there was no significant interaction between time and serum type, nor between serum type and the test performed. Regarding the concentration of molecules, in our study AS contained significantly higher concentrations of IgA, IgG and fibronectin whereas HS contained significantly higher concentration of IgM, vitamins A and E, TGF and albumin. Contrary to previous reports, CS did not show higher concentration of any of the molecules analysed. CONCLUSIONS AND RELEVANCE: The three sera were effective in the treatment of severe DES. CS did not contain a higher proportion of molecules compared to AS/HS. More research is needed to assess the effect of AS in patients with DES and autoimmune diseases.

Anterior segment involvement in Epstein-Barr virus: a review.

The aim of this study is to describe the involvement of Epstein-Barr Virus (EBV) in the diseases of the ocular anterior segment. This is a narrative review designed using the PUBMED, SCOPE and Web of Science databases, searching for reported literature on findings in the anterior ocular segment related to EBV between 1990 and 2020. Epstein-Barr Virus (EBV) is implicated in the development of salmon-coloured conjunctival masses in the context of acute mononucleosis and lymphoproliferative disorders. Moreover, EBV can cause haemorrhagic conjunctivitis and its corneal implications appear as different types of keratitis patterns. The involvement of EBV in the pathogenesis of anterior segment inflammation is not well-defined. Current evidence regarding anterior segment disease caused by EBV infection has been proved by positive viral detection through polymerase chain reaction test in eyes with lymphoproliferative disorders known to be caused by EBV, as B- and NK/T-cell lymphoid tumours. Antiviral treatment (oral Aciclovir or Valaciclovir) in anterior segment disease caused by EBV remains controversial.

Ocular side effects of checkpoint inhibitors.

The incidence and impact of ocular side effects in patients treated with checkpoint inhibitors are not clearly defined. We reviewed prospective phase III clinical trials of checkpoint inhibitors applied in lung cancer, renal cell cancer, and melanoma. Case reports of the occurrence of ocular toxicities in patients receiving immune checkpoint inhibitors were also included. Of the 35 articles corresponding to phase III clinical trials with checkpoint inhibitors, ocular toxicity was described in four. Forty-six clinical cases of ocular toxicity after therapy with checkpoint inhibitors have been reported. The most frequently described ocular toxicities are uveitis, inflammatory orbital disease, and alterations of the ocular surface. Ocular toxicity is underestimated in checkpoint inhibitors clinical trials. Early ophthalmic examination and treatment with corticosteroids may improve the visual prognosis in these patients.

Adalimumab in Elderly Patients with Non-Infectious Uveitis. Safety and Efficacy.

Purpose: To assess the efficacy and safety of adalimumab in elderly patients with noninfectious uveitis (NIU).Methods: An observational, retrospective, multicenter study was done. Changes in best-corrected visual acuity (BCVA), inflammatory activity parameters, central retinal thickness (CRT), and the occurrence of adverse events (AE) developed during follow-up were recorded.Results: A total of 82 eyes from 41 patients 60 years of age and older with noninfectious uveitis treated with adalimumab were included. A significant improvement in BCVA (71.5 to 75.4 letters, p = .001) and in CRT (311.1 µm to 265 µm, p = .001) was observed. Moreover, a significant decrease from baseline in the rate of patients with anterior chamber cell (ACC) >0+ (34.6% to 5.7%, p = <0.001) or vitreous haze>0+ (21.3% to 4.3%, p = .002) was determined. AEs were observed in 11 patients (26.8%).Conclusion: Adalimumab can be safe and efficacious for the treatment of NIU in patients 60 years of age and older.

Use of ultra-wide field retinal imaging and optical coherence tomography angiography in the diagnosis of incomplete Susac syndrome.

PURPOSE: To describe clinical findings through ultra-wide field (UWF) images and optical coherence tomography angiography (OCT-A), in Susac's syndrome (SS). METHODS: SS patients were retrospectively analyzed in a single center. Clinical features, ultra-wide-field retinographies (UWF-PR), UWF fluorescein angiographies (UWF-FA), and optical coherence tomography angiography & en face (OCT-A/EF) were reviewed. RESULTS: Twelve eyes from six patients with a mean follow-up of 35.66 months ± SD 36.88 were included. UWF-PR showed areas of retinal whitening and cotton-wool spots in all the eyes after acute attack. Segmentary mid peripheral arteriolitis could be observed in five eyes by UWF-FA in acute and convalescent stages. OCT-A revealed capillary density changes in all of the affected eyes. During the acute phase there was a well-preserved superficial capillary network, while deep retinal plexus showed a lower density in the affected areas. OCT-A/EF revealed deep retinal plexus drop-out and surrounding edematous retina in acute attacks, becoming atrophic over time. Conversely, superficial plexus was much less affected. Perifoveal reperfusion was seen in seven eyes after the acute attack. CONCLUSIONS: UWF-PR/FA and OCT-A/EF might be helpful to stablish an early diagnosis and to monitor SS progression.

Tomographic and aberrometric assessment of first-time diagnosed paediatric keratoconus based on age ranges: a multicentre study.

PURPOSE: To describe paediatric keratoconus (KC) patients by tomographic and aberrometric characteristics at first diagnosis, in a multicentre study. METHODS: We included 278 eyes from 139 paediatric patients, with a first tomographic diagnosis (Pentacam® ) of KC prior to 18 years old. KC classification was based on the KC Index (≥ 1.07) and Topographic Keratoconus Classification (TKC ≥ 1). Patients were divided based on age ranges (14 and under and over 14 years) and gender. Statistical analysis was performed with SPSS statistics 25.0. ANOVA factor was carried out comparing to compare groups. RESULTS: 278 eyes were screened, and 230 eyes were diagnosed with paediatric KC. Mean age was 15.48 ± 2.33 (6 to 18) years. We found differences in terms of TKC (2.08 ± 0.89 and 2.38 ± 0.82, p < 0.05) and spherical aberration (-0.71 ± 0.97 and -1.07 ± 1.36, p < 0.05) among the 14 years old or under and above 14 years old groups, respectively. Overall, female paediatric KC patients presented a more severe TKC, Belin Ambrosio Display, maximum keratometry, asphericity and primary and secondary coma aberrations compared to male KC patients. We observed a correlation between CDVA and asphericity (r = 0.71, p < 0.01), as well as between CDVA and spherical aberration (r = 0.69, p < 0.01). CONCLUSION: Our findings revealed that the debut of KC is usually in a moderate to advanced stage in the paediatric population at first diagnosis, particularly in female patients. Corneal tomography should be systematically performed in children with recent onset of corneal astigmatism.

Uveitic macular edema response to intravitreal dexamethasone implant is independent of optical coherence tomography findings.

PURPOSE: To identify predictive response optical coherence tomography (OCT) findings in uveitic macular edema (UME) treated with intravitreal dexamethasone implant (DEX). METHODS: Retrospective study of 66 eyes (53 patients) treated with DEX for UME. SD-OCT macular scans were collected prior to DEX treatment and 6 weeks and 3 months after the DEX implant. OCT images were evaluated for qualitative and quantitative characteristics (central retinal thickness, CRT and macular volume, MV). A multivariate analysis of covariance (ANCOVA) was carried out to study the predictive influence of OCT and clinical covariates on outcomes. The main outcome was a composite endpoint based on the simultaneous gain of 5 or more letters associated with a 20% or more reduction in CRT. RESULTS: A significant improvement in BCVA at 6 weeks (mean change from baseline -0.2, SD 0.3) and 3 months (mean -0.2, SD 0.4) was observed after the DEX implant. A significant decrease in CRT (change from baseline -187.7 µm at 3 months) and MV (change from baseline -1.7 mm3 at 3 months) were also observed. An association of ≥ 5-letter improvement in BCVA and a ≥ 20% CRT reduction was observed in 44.6% of cases at 6 weeks and 31.4% at 3 months. ANCOVA multivariate analyses found CRT at 3 months independent from baseline clinical variables but from CRT. CONCLUSION: DEX implant is an effective treatment for UME independently of basal characteristics, producing both a gain of visual acuity and improvement of macular anatomy by OCT measures at 3 months.

Ocular surface characterization after allogeneic stem cell transplantation: A prospective study in a referral center.

Purpose: To characterize anatomical and functional changes in the ocular surface after hematopoietic stem cell transplantation. Methods: Three groups of patients were included in the study. Group 1: patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT) (n = 26). Group 2: patients who developed chronic graft versus host disease (GvHD) after HSCT (n = 14). Group 3: healthy subjects (n = 20). A complete ophthalmological examination was undertaken in all subjects, including Schirmer's test, TBUT (break-up-time) test, Oxford scale, OSDI test, corneal tomography, and conjunctival CD8+ lymphocyte detection. Results: In Branch 1 (comparative analysis before and after HSCT in Group 1), statistically significant differences were found in the following variables: best-corrected visual acuity (BCVA) OD (P = 0.08), OSDI test (P = 0.003), TBUT OU (OD P= 0, OS P= 0.0003), Oxford test OU (OD P= 0.01, OS P= 0.0049), and CD8+ lymphocytes OU (OD P= 0.003, OS P= 0.01). In Branch 2 (comparative analysis between Group 2 and 3), the variables with statistically significant differences (P < 0.001) in OU were: BCVA, OSDI test, Schirmer's test OU, TBUT test, Oxford test, and CD8+ lymphocytes. Finally, in Branch 3 (comparative analysis between Group 1 after HSCT and Group 2), statistically significant differences (P < 0.001) were found OU: in OSDI test, Schirmer's test, and Oxford test OU; and with P < 0.005 in TBUT test OU. Conclusion: In our study, statistically significant changes were observed in the OSDI test, TBUT test, Oxford Scale, and the detection of CD8+ lymphocytes in patients who underwent HSCT. Differences were more significant in those patients who had developed GvHD after HSCT compared to those without GvHD.

Relapsed ocular squamous surface neoplasia treated with topical interferon alfa-2b.

A 54-year-old patient presented with a large, fleshy conjunctival lesion in the right eye that had been previously surgically removed in another centre. Diagnosis of Conjunctival intraepithelial neoplasia (CIN) was confirmed by conjunctival impression cytology. The tumor was treated with topical IFN-α-2ß (1,000,000 IU/ (ml) adjuvant to surgery for chemoreduction purposes. One month after treatment, the lesion showed almost complete involution, therefore the treatment was continued up to 6 months, and the lesion showed full regression. The patient is currently under periodical follow-up by conjunctival impression cytology. We consider that topical IFN-α-2ß can be used in CIN for chemoreduction and/ or curative purposes. We believe that conjunctival impression cytology is a useful and non-invasive method for diagnosis and follow-up in this condition.

Long-Term Intravitreal Dexamethasone Implant Outcomes in Uveitis.

Purpose: To describe the long-term clinical outcomes in a cohort of uveitic eyes treated with the intravitreal dexamethasone implant (Ozurdex; Allergan, Inc).Methods: Seventy-nine (63 patients) receiving 134 implant injections over 82 months were included. Indication, visual acuity (VA), intraocular pressure (IOP), vitreous haze score (VHS), central retinal thickness (CRT), time to reinjection, systemic treatments, and complications data were recorded.Results: The cumulative probability of VA improvement was 80% at 1 month and 90% at 12 months, and it was maintained until 60 months. Eyes with baseline vitritis (VHS >0.5; 68%) had a probability of VHS improvement of 33% at 1 month, 75% at 12 months, and 85% at 60 months. The probability of CRT improvement was 33% at 1 month, 75% at 12 months, and 85% at 60 months. The most frequent adverse event was moderate IOP elevation (≥25 mmHg) in 30.3%, no cases of retinal detachment or endophthalmitis were observed.Conclusions: The dexamethasone implant provides favorable VA, CRT, and VHS long-term outcomes in uveitis with a reduced rate of severe adverse events.