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PURPOSE: To provide an overview of the ocular features of rheumatoid arthritis (RA) and of the ophthalmic adverse drug reactions (ADRs) that may be associated with the administration of antirheumatic drugs. METHODS: A systematic literature search was performed using the PubMed, MEDLINE, and EMBASE databases. In addition, a cohort of 489 RA patients who attended the Authors' departments were examined. RESULTS: Keratoconjunctivitis sicca, episcleritis, scleritis, peripheral ulcerative keratitis (PUK), and anterior uveitis were diagnosed in 29%, 6%, 5%, 2%, and 10%, respectively, of the mentioned cohort. Ocular ADRs to non-steroidal anti-inflammatory drugs are rarely reported and include subconjunctival hemorrhages and hemorrhagic retinopathy. In patients taking indomethacin, whorl-like corneal deposits and pigmentary retinopathy have been observed. Glucocorticoids are frequently responsible for posterior subcapsular cataracts and open-angle glaucoma. Methotrexate, the prototype of disease-modifying antirheumatic drugs (DMARDs), has been associated with the onset of ischemic optic neuropathy, retinal cotton-wool spots, and orbital non-Hodgkin's lymphoma. Mild cystoid macular edema and punctate keratitis in patients treated with leflunomide have been occasionally reported. The most frequently occurring ADR of hydroxychloroquine is vortex keratopathy, which may progress to "bull's eye" maculopathy. Patients taking tofacitinib, a synthetic DMARD, more frequently suffer herpes zoster virus (HZV) reactivation, including ophthalmic HZ. Tumor necrosis factor inhibitors have been associated with the paradoxical onset or recurrence of uveitis or sarcoidosis, as well as optic neuritis, demyelinating optic neuropathy, chiasmopathy, and oculomotor palsy. Recurrent episodes of PUK, multiple cotton-wool spots, and retinal hemorrhages have occasionally been reported in patients given tocilizumab, that may also be associated with HZV reactivation, possibly involving the eye. Finally, rituximab, an anti-CD20 monoclonal antibody, has rarely been associated with necrotizing scleritis, macular edema, and visual impairment. CONCLUSION: The level of evidence for most of the drug reactions described herein is restricted to the "likely" or "possible" rather than to the "certain" category. However, the lack of biomarkers indicative of the potential risk of ocular ADRs hinders their prevention and emphasizes the need for an accurate risk vs. benefit assessment of these therapies for each patient.
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Antirreumáticos , Artritis Reumatoide , Glaucoma de Ángulo Abierto , Antirreumáticos/efectos adversos , Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Glaucoma de Ángulo Abierto/complicaciones , Humanos , Enfermedad Iatrogénica , RituximabRESUMEN
BACKGROUND: Posterior uveitis represents the second most frequent type of uveitis (15-30% of all uveitis). Noninfectious posterior uveitis complicated with secondary cystoid macular edema (CME) affects the visual prognosis negatively. The objective of the current study is to detect possible microvascular changes causing relapsing uveitis-related CME using optical coherence tomography angiography (OCTA). METHODS: This is an interventional, observational, retrospective study with 1 year follow-up. Patients with noninfectious, posterior uveitis-related CME undergoing dexamethasone (DEX) implant were evaluated. Following the DEX-implant were carried out control visits after 1 month, 2-months, 4-months, 6-months, and for up 1-year. A total of 76 eyes of 38 consecutive patients with noninfectious posterior uveitis were enrolled (consecutive sample). Complicated noninfectious posterior uveitis with secondary CME was diagnosed in 56 eyes of uveitis patients (73.7%) and reviewed. RESULTS: Our investigation showed (1) a reduction in superficial vessel plexus (SVP) measurements within 2-month (84%), reaching 96.4% for up 1-year, (2) an irregular profile of SVP in 69.6% of cases, persisting for up 1-year; relapsing uveitis-related CME eyes with irregular superficial foveal avascular zone (FAZ) profile were in 51%, while the SVP measurements reestablished in 100% of cases. Conversely, (3) the deep vascular plexus (DVP) parameters restored in a lower number of eyes within the 2-month (39.3%), remaining abnormal in 46.4% of cases for up 1-year; despite DVP restored in 53.6% of cases for up 1 year, (4) a capillary rarefaction ring around the FAZ appeared in 80.4% of cases; the relapsing uveitis-related CME eyes with abnormal DVP parameters were present in 41% of cases, of which 92.1% showed a rarefaction ring had abnormal DVP. CONCLUSIONS: The use of OCTA enabled the evaluation in detail of retinal microvascular changes. We suggested that the possibility of the recurrence of the uveitis-related CME depends on the persistence of modifications of the superficial and deep layers. In this regard, we propose to implement the current imaging armamentarium with OCTA for the follow-up of patients with noninfectious uveitis-related CME.
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Edema Macular , Uveítis Posterior , Uveítis , Humanos , Edema Macular/etiología , Edema Macular/complicaciones , Tomografía de Coherencia Óptica/métodos , Angiografía con Fluoresceína/métodos , Vasos Retinianos , Estudios Retrospectivos , Agudeza Visual , Recurrencia Local de Neoplasia , Uveítis Posterior/complicaciones , Uveítis/complicaciones , Uveítis/diagnóstico , DexametasonaRESUMEN
OBJECTIVES: To assess the efficacy of anti-tumour necrosis factor (TNF)-α agents in the treatment of refractory uveitic macular oedema (UME). METHODS: Patients with refractory UME treated with TNF-α blockers were retrospectively enrolled. Central macular thickness (CMT) was assessed at optical coherence tomography (OCT) at the start of TNF-α inhibition, after 3 and 12 months, and at the last follow-up visit. RESULTS: Thirty-six patients (56 eyes with UME) were enrolled. The mean follow-up period was 29.9±40.8 (4-184) months. A statistically significant decrease was observed in the frequency of UME (p<0.0001) and in the mean CMT values (p<0.0001) during the study period. Best corrected visual acuity improved in 35 eyes (62.5%), remained stable in 12 eyes (21.4%), reduced in 9 eyes (16.1%). The mean corticosteroid dosage significantly decreased during the study period (p=0.016). CONCLUSIONS: TNF-α inhibitors represent a useful treatment in patients with severe or resistant UME.
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Edema Macular , Estudios de Seguimiento , Humanos , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa , Agudeza VisualRESUMEN
OBJECTIVES: To evaluate the efficacy of tumour necrosis factor (TNF)-α inhibitors in refractory non-infectious scleritis. METHODS: We carried out a retrospective study assessing the efficacy of TNF-α inhibitors in the treatment of scleritis, scleritis relapses, glucocorticoid (GC)-sparing effect, impact on best-corrected visual acuity (BCVA) and safety profile. RESULTS: Nineteen patients (28 eyes) were eligible for analysis. Scleritis inflammatory grading significantly improved from baseline to the last follow-up (median ± IQR 2±4 and 0±0 respectively, p=0.0006). Scleritis relapses significantly decreased between the 12 months preceding and following biologic therapy (p=0.001). Mean GC dosage decreased from baseline (19.00±13.56 mg) to the last follow-up (7.59±5.56 mg) (p=0.003). No significant differences regarding BCVA were observed. Two AEs were recorded (1 severe urticaria and 1 case of pneumonia and paradoxical psoriasis). CONCLUSIONS: TNF-α inhibitors are effective in the treatment of scleritis while allowing a GC-sparing effect and preserving BCVA.
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Escleritis , Factor de Necrosis Tumoral alfa , Humanos , Estudios Retrospectivos , Escleritis/diagnóstico , Escleritis/tratamiento farmacológico , Resultado del Tratamiento , Agudeza VisualRESUMEN
OBJECTIVE: To assess the efficacy of biologic drugs, beyond tumor necrosis factor- (TNF-) α inhibitors, in the management of noninfectious refractory scleritis, either idiopathic or associated with systemic immune-mediated disorders. Patients and Methods. This is a retrospective study assessing the efficacy of several biologic agents (rituximab, anakinra, tocilizumab, and abatacept) and the small molecule tofacitinib in the treatment of scleritis through assessment of scleral inflammation and relapses, as well as treatment impact on best-corrected visual acuity (BCVA) and safety profile. RESULTS: Fourteen patients (19 eyes) were enrolled in the study. Scleritis inflammatory grading significantly improved from baseline to 3 months (p = 0.002) and from baseline to the last follow-up visit (p = 0.002). Scleritis relapses significantly decreased between the 12 months preceding and following biologic therapy (p = 0.007). No differences regarding BCVA were observed (p = 0.67). Regarding adverse events, only one patient developed pneumonia and septic shock under rituximab treatment. CONCLUSIONS: Our results, though limited to a low number of patients, highlight the effectiveness of different biologic therapies in the treatment of noninfectious refractory scleritis, showing to control scleral inflammation and allowing a significant reduction in the number of relapses.
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Antineoplásicos Inmunológicos/farmacología , Escleritis/inducido químicamente , Escleritis/tratamiento farmacológico , Abatacept/farmacología , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/farmacología , Femenino , Humanos , Sistema Inmunológico , Inflamación , Proteína Antagonista del Receptor de Interleucina 1/farmacología , Masculino , Persona de Mediana Edad , Oftalmología , Piperidinas/farmacología , Pirimidinas/farmacología , Recurrencia , Estudios Retrospectivos , Rituximab/farmacología , Resultado del TratamientoRESUMEN
PURPOSE: To propose a modified ophthalmic triage system based on simple ophthalmic symptoms, signs and anamnestic data and validate its safety and effectiveness. METHODS: Phase 1 of the study was a retrospective review of chart records of patients admitted at the ophthalmic emergencies room (OER); phase 2 was a prospective study conducted on all consecutive patients presenting in the OER between April 1st, 2018, and May 30th, 2018. We selected the following six factors as predictors of urgency levels: altered vision, ocular behavior, color, distress, eye trauma, floaters and flashes. ATSO final score can be eventually converted into risk groups: low-risk group (scoring 0-3), intermediate-risk group (scoring 4-5) and high-risk group (scoring > 6). RESULTS: A total of 953 consecutive patients who presented to our OER over a two-month period were considered for participation in the study. The male-to-female ratio was 1.24:1. The mean age of the participants was 53 years (range 18-92, SD 19 years). ATSO score significantly correlated with urgency levels (p < .00001). The sensitivity of ATSO in differentiating urgent from non-urgent conditions was 91.4%, and the specificity was 98.2%. All hospitalized patients (30, 3.15%) have been coded as intermediate/high risk according to the ATSO score. CONCLUSION: The use of the ATSO score for patients at the OER provides the clinician with a reliable predictor of urgency, being at the same time safe and effective. The ATSO score may represent a valuable tool to implement triage of ocular patients in the emergency department.
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Oftalmología , Triaje , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Urgencias Médicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: To assess the efficacy of monoclonal anti-tumour necrosis factor (TNF)-α agents in patients with anterior uveitis (AU) in terms of decrease of recurrences, variation of visual acuity and steroid sparing effect and to identify any demographic, clinical or therapeutic variables associated with a sustained response to monoclonal TNF-α inhibitors. METHODS: Data from patients suffering from AU treated with adalimumab, infliximab, golimumab or certolizumab pegol were retrospectively collected and statistically analysed. RESULTS: Sixty-nine patients (22 males, 47 females), corresponding to 101 eyes, were enrolled. The mean follow-up period was 29.25±23.51 months. The rate of ocular flares decreased from 42.03 events/100 patients/year recorded during the 12 months preceding the start of TNF-α inhibitors to 2.9 flares/100 patients/year after the start of treatment (p<0.0001). The overall decrease in ocular flares was 93.1%. No statistically significant changes were identified in the best corrected visual acuity during the follow-up period (p>0.99). The number of patients treated with corticosteroids at baseline was significantly higher compared with that referred to the 12-month evaluation (p<0.001) and to the last follow-up visit (p=0.006). Concomitant treatment with conventional disease-modifying anti-rheumatic drugs (cDMARDs) represented the sole clinical, demographic or therapeutic variable associated with long-term treatment duration (p=0.045, R2=0.87). CONCLUSIONS: Monoclonal TNF-α inhibitors induce a remarkable decrease in the recurrence of AU during a long-term follow-up period and lead to a significant steroid sparing effect along with stabilisation of visual acuity. Concomitant treatment with cDMARDs represented the sole variable associated with treatment duration in the long-term.
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Antirreumáticos/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Uveítis Anterior/tratamiento farmacológico , Adalimumab , Anticuerpos Monoclonales , Femenino , Humanos , Infliximab , Masculino , Estudios Retrospectivos , Brote de los Síntomas , Resultado del Tratamiento , Uveítis Anterior/inmunologíaRESUMEN
OBJECTIVES: The aim of the study was to evaluate the efficacy of golimumab (GOL) and certolizumab pegol (CZP) as additional treatment options for the treatment of uveitis. METHODS: Patients with longstanding uveitis receiving either GOL or CZP were retrospectively evaluated in terms of frequency of ocular flares, drug survival, changes in best corrected visual acuity (BCVA) and steroid-sparing effect. RESULTS: Twenty-one patients (30 eyes), 17 of whom being female, were enrolled in the study; 16 out of 21 patients had been previously treated with other tumour necrosis factor (TNF)-α blockers. A significant reduction in ocular flares (from 128.6 bouts for 100 patients-year to 42.9 events for 100 patients-year) was observed between the 12 months prior to the start of GOL or CZP and the 12 months thereafter (p=0.01). The 36-month drug survival was 54.5% for CZP and 50.0% for GOL with no statistically significant differences between the two biologic agents. No differences were detected concerning BCVA values and the mean corticosteroid intake between baseline and the last follow-up. The safety profile was excellent. CONCLUSIONS: GOL and CZP represent effective and safe treatment choices for patients with uveitis also when unsuccessfully treated with other anti-TNF-α drugs, permitting a significant reduction in the frequency of ocular flares and preserving visual function with a good long-term retention rate.
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Factor de Necrosis Tumoral alfa , Uveítis/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Certolizumab Pegol/efectos de la radiación , Femenino , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/uso terapéuticoRESUMEN
BACKGROUND: Leber's hereditary optic neuropathy (LHON) associated with mutations in mitochondrial DNA (mtDNA) typically manifests only optic nerve involvement but in some patients may develop additional neurological complications. The cause of this association is not clear. CASE PRESENTATION: We present a case of a 24-year-old male with a history of subacute, painless, and rapidly progressive bilateral vision loss. We performed ophthalmological, neurological and neuropsychological investigations in the proband and his LHON family. The proband showed optic neuropathy, epilepsy, migraine, and intellectual disability; all the maternal relatives did not manifest optic neuropathy but a moderate to severe intellectual disability. Genetic screening revealed a novel association of the LHON m.3460G > A primary mutation with the m.T961delT + C(n)ins within the mitochondrial encoded 12S RNA (MTRNR1) gene which segregates with the intellectual disability through the maternal branch of the family. We also found a significant increase of mtDNA content in all the unaffected homo/heteroplasmic mutation carriers with respect to either affected or control subjects. CONCLUSION: This is the first case reporting the co-segregation of a mutation in MTRNR1 gene with a LHON primary mutation, which may be a risk factor of the extraocular signs complicating LHON phenotype. In addition, the data herein reported, confirmed that the key factor modulating the penetrance of optic atrophy in the family is the amount of mtDNA.
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ADN Mitocondrial/genética , Epilepsia/genética , Discapacidad Intelectual/genética , Mutación/genética , Atrofia Óptica Hereditaria de Leber/genética , ARN Ribosómico/genética , Adulto , Anciano , Femenino , Humanos , Masculino , Repeticiones de Microsatélite/genética , Persona de Mediana Edad , Mitocondrias/genética , Linaje , Penetrancia , Adulto JovenRESUMEN
OBJECTIVES: To describe the epidemiology of non-infectious uveitis (NIU) in two tertiary referral rheumatology units in Central and Southern Italy. METHODS: Two hundred and seventy-eight consecutive NIU patients (417 eyes) evaluated between January 2016 and January 2017 were enrolled. Collected data were analysed in accordance with the primary anatomic site of inflammation, clinical course, and laterality. RESULTS: The mean age at NIU onset was 36.92±18.30 years with a female-to-male ratio of 1.34:1. Anterior uveitis (AU) was identified in 151 (54.32%), posterior uveitis (PU) in 67 (24.10%), intermediate uveitis (IU) in 5.40% and panuveitis (PanU) in 16.19% patients. Bilateral involvement was identified in 50% of our cohort. Uveitis was acute in 33.81% of patients, while 24.46% and 41.73% had a chronic and recurrent course, respectively. Gender and laterality did not influence the anatomical pattern, while disease course was significantly more acute or chronic in AU (p<0.05) and chronic in IU (p<0.05). An associated systemic disease was identified in 116 patients (41.73%). Twenty-seven patients (9.7%) had a specific isolated eye disease, 135 patients (48.56%) had idiopathic NIU. Uveitis associated with a systemic disease was significantly bilateral (p=0.01) and acute or chronic (p<0.0001), while the isolated form showed an association with chronic course (p<0.0001) and unilaterality (p=0.01). CONCLUSIONS: The most common anatomic pattern of NIU has been AU, followed by PU, PanU and IU. A systemic disease (mainly Behçet's disease, ankylosing spondylitis and juvenile idiopathic arthritis) has been recognised in a fair proportion of the entire cohort. The rheumatologist should remain a central professional figure in the multidisciplinary team dealing with intraocular inflammation on a daily basis.
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Panuveítis/epidemiología , Reumatólogos , Reumatología , Centros de Atención Terciaria , Adolescente , Adulto , Femenino , Encuestas Epidemiológicas , Humanos , Italia , Masculino , Persona de Mediana Edad , Panuveítis/diagnóstico , Panuveítis/terapia , Pronóstico , Estudios Retrospectivos , Factores de Tiempo , Uveítis Anterior/diagnóstico , Uveítis Anterior/epidemiología , Uveítis Posterior/diagnóstico , Uveítis Posterior/epidemiología , Adulto JovenRESUMEN
We describe a case of keratitis caused by Paecilomyces lilacinus in a contact lens wearer with a history of diabetes.
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Lentes de Contacto Hidrofílicos/efectos adversos , Córnea/microbiología , Contaminación de Equipos , Infecciones Fúngicas del Ojo/etiología , Queratitis/etiología , Paecilomyces/aislamiento & purificación , Lentes de Contacto Hidrofílicos/microbiología , Córnea/patología , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/microbiología , Humanos , Queratitis/diagnóstico , Queratitis/microbiología , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The evidence on the use of dexamethasone implants in the treatment of Behçet's disease (BD)-related uveitis is limited to a few cases. OBJECTIVES: To evaluate the efficacy of dexamethasone implants on ocular functional, morphological, and clinical parameters in BD patients with severe refractory uveitis. METHODS: Five eyes from five BD patients were enrolled. A single intravitreal dexamethasone injection was applied to each eye. Best corrected visual acuity (BCVA), central macular thickness (CMT) assessed with optical coherence tomography, retinal vasculitis assessed by fluorescein angiography, vitreous haze score (Nussenblatt scale), intraocular pressure (IOP), and lens status (LOCS III, Lens Opacities Classification System III) were recorded at baseline and at 1, 3, and 6 month follow-up visits. RESULTS: At baseline, all eyes showed marked macular edema and 4/5 had concomitant active retinal vasculitis. Mean BCVA was increased from baseline at each control visit with a mean improvement of 0.26 ± 0.18 lines at 6 months follow-up. Mean CMT decreased from baseline at each control visit with a mean improvement at 6 months follow-up of 198.80 ± 80.08 µm. At the end of the study, none of the eyes showed macular edema and the mean CMT was 276.80 ± 24.94 µm. Retinal vasculitis resolved in all eyes. One eye experienced an IOP spike during treatment that resolved spontaneously, and one eye developed a clinically significant lens opacity at 6 months follow-up. CONCLUSIONS: Treatment with a dexamethasone implant in BD-uveitis and inflammatory macular edema was safe and effective as an additional treatment combined with systemic immunomodulatory drugs.
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Síndrome de Behçet/complicaciones , Dexametasona/administración & dosificación , Implantes de Medicamentos/administración & dosificación , Glucocorticoides/administración & dosificación , Edema Macular/tratamiento farmacológico , Uveítis/tratamiento farmacológico , Humanos , Inyecciones Intravítreas , Edema Macular/etiología , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Uveítis/etiología , Agudeza VisualRESUMEN
OBJECTIVES: The purpose of the present study was to describe our experience with the recombinant Fab' antibody fragment against TNF-α Certolizumab Pegol (CZP) in patients with Behçet's disease (BD) refractory to standardized therapies and previous biologic agents. METHODS: Retrieved data including demographic characteristics, clinical manifestations, and previous treatments were collected in three different specialized Rheumatologic Units in Italy. In order to evaluate disease activity, the BD current activity form (BDCAF) has been used before starting CZP therapy and at each visit during treatment. RESULTS: Thirteen BD patients (mean age 42.6 ± 8.8 years) with a disease duration of 8.80 ± 6.9 years, underwent CZP treatment for 6.92 ± 3.52 months. Six patients (46.15%) experienced a worsening of symptoms after 4.16 ± 1.21 months, whereas a satisfactory response was achieved in seven patients (53.84%) who were still on CZP therapy at the last follow-up visit (after 9.28 ± 3.03 months of treatment). The mean decrease of BDCAF between the first and last visit was 0.308 ± 1.84 without reaching significant difference (mean 8.3 ± 1.3 and 8 ± 2.08, respectively; p= .51). During the whole study period, CZP was well tolerated in all patients except one who developed a generalized cutaneous reaction after the third administration. CONCLUSIONS: These results suggest that despite an improvement of clinical manifestations has been observed in more than half of the patients, it is not possible to draw firm conclusions about the effectiveness of CZP in BD and further studies with larger cohorts of patients are warranted. Whether the increase of CZP dosage may ensure a better clinical response remains an unsolved issue that needs to be considered.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/uso terapéutico , Síndrome de Behçet/tratamiento farmacológico , Certolizumab Pegol/uso terapéutico , Adulto , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Certolizumab Pegol/administración & dosificación , Certolizumab Pegol/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
OBJECTIVE: To report a case of fungal keratitis caused by Alternaria in a 49-year-old female who developed an acute onset of eye infection after ocular trauma caused by an olive leaf. METHODS: The clinical presentation, microbiological diagnosis, and therapeutic approaches are reported. RESULTS: The patient was referred to our university hospital clinic with corneal abscess in her left eye. Before the start of an empirical antibacterial therapy (both topical and systemic), a swab of the cornea was obtained which at microscopic examination revealed a few fragments of hyphal elements, probably for the paucity of material collected. After one week, the corneal abscess had increased in size, and the corneal stroma was filled with filamentous structures similar to fungal hyphae. Oral and topical voriconazole was administered because of the clinical picture and the response of microbiological laboratory whose examination of the material removed from the anterior chamber showed numerous hyphal fragments identified by culture as Alternaria spp. The corneal abscess healed in two weeks, but the patient now has a corneal scar and is awaiting a corneal transplant. CONCLUSIONS: Ophthalmologists and microbiologists must take fungi into greater consideration as a possible cause of keratitis as they are emerging as the cause of this infectious disease in many countries. Voriconazole spreads well in the eye and is effective in the cure of fungal keratitis including those caused by Alternaria.
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Alternaria/aislamiento & purificación , Alternariosis/complicaciones , Úlcera de la Córnea/microbiología , Infecciones Fúngicas del Ojo/microbiología , Lesiones Oculares/complicaciones , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Leber's hereditary optic neuropathy (LHON) is associated with mitochondrial DNA (mtDNA) ND mutations that are mostly homoplasmic. However, these mutations are not sufficient to explain the peculiar features of penetrance and the tissue-specific expression of the disease and are believed to be causative in association with unknown environmental or other genetic factors. Discerning between clear-cut pathogenetic variants, such as those that appear to be heteroplasmic, and less penetrant variants, such as the homoplasmic, remains a challenging issue that we have addressed here using next-generation sequencing approach. We set up a protocol to quantify MTND5 heteroplasmy levels in a family in which the proband manifests a LHON phenotype. Furthermore, to study this mtDNA haplotype, we applied the cybridization protocol. The results demonstrate that the mutations are mostly homoplasmic, whereas the suspected heteroplasmic feature of the observed mutations is due to the co-amplification of Nuclear mitochondrial Sequences.
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Núcleo Celular/genética , ADN Mitocondrial/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mitocondrias/genética , Mutación/genética , Atrofia Óptica Hereditaria de Leber/genética , Adenosina Trifosfato/biosíntesis , Adolescente , Adulto , Complejo I de Transporte de Electrón/genética , Metabolismo Energético , Femenino , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Masculino , Persona de Mediana Edad , Proteínas Mitocondriales/genética , Linaje , Temperatura , Adulto JovenRESUMEN
Chronic diseases are a growing problem for global health due to the large number of people they involve, the repercussions they have on the mental and physical well-being of those affected, and the costs to society. Particularly, chronic illnesses of childhood have important psychological implications, not only for affected children but also for their parents. Among these pathologies, neurodevelopmental disorders (NDDs) and uveitis associated with juvenile idiopathic arthritis (JIA-U) may affect mental and physical health, emotions, memory, learning, and socializing. This study evaluates the psychological and behavioral/emotional impact of NDDs and JIA-U on children and parents. Specifically, 30 children with active JIA-U and 30 children with NDDs and their parents completed the Child Behavior Checklist (CBCL) and Parent Stress Index-Short Form (PSI) questionnaires. Children with NDDs have statistically significant differences in all the emotional and behavioral variables compared to JIA-U children, and parents of children with NDDs experience an increased stress load compared to parents of children with JIA-U. This study emphasizes the wide range of emotional and behavioral challenges that parents face with NDDs. This study emphasizes that parents of children with NDDs not only experience higher levels of stress compared to parents of normally developing children but also experience higher levels of stress compared to parents of children with potentially debilitating chronic diseases such as JIA-U.
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Purpose: To compare radial peripapillary capillary (RPC) vascular plexus parameters and peripapillary retinal nerve fiber layer (pRNFL) thickness between Early-Treated Adults with Phenylketonuria (ETPKU) and controls. Methods: This observational study was a monocentric, case control study including 36 eyes of 36 participants. Among these, 18 were early-treated PKU (ETPKU) and 18 were controls. A SD-OCTA (XR Avanti AngioVue OCTA; Optovue Inc., Fremont, CA) was employed to assess the OCT and OCTA parameters of all the participants. The main outcome measures were the RPC vessels density (VD) %, and the pRNFL thickness. Results: The average pRNFL thickness was significantly reduced in ETPKU (110.78 ± 12.48 µm) compared to controls (113.22 ± 13.95 µm), p = 0.046. The mean VD% of the small vessels of the RPC plexus was 52.31 ± 2.2 in ETPKU and 50.71 ± 3.2 in controls (p = 0.049), while the VD% of all the radial peripapillary capillary plexus (RPCP) was 58.5 ± 2.2 in ETPKU and 55.08 ± 3.4 in controls (p < 0.001). By contrast, there were no differences in age, sex, and IOP between the two groups. Conclusion: Through structural OCT and OCTA, we observed thinning of the nerve fibers accompanied by an increase in perfusion of the RPC plexus. Thus, our conclusions suggest that OCTA may serve as a noninvasive method to identify novel retinal biomarkers in ETPKU.
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INTRODUCTION: This study aims to characterize ocular manifestations of juvenile Behçet's disease (jBD). METHODS: This was a registry-based observational prospective study. All subjects with jBD from the Autoinflammatory Diseases Alliance (AIDA) Network BD Registry showing ocular manifestations before 18 years were enrolled. RESULTS: We included 27 of 1000 subjects enrolled in the registry (66.7% male patients, 45 affected eyes). The median (interquartile range [IQR]) age at ocular involvement was 14.2 (4.7) years. Uveitis affected 91.1% of eyes (anterior 11.1%, posterior 40.0%, panuveitis 40.0%), retinal vasculitis 37.8% and other manifestations 19.8%. Later onset (p = 0.01) and male predominance (p = 0.04) characterized posterior involvement. Ocular complications occurred in 51.1% of eyes. Patients with complications had earlier onset (p < 0.01), more relapses (p = 0.02) and more prolonged steroidal treatment (p = 0.02). The mean (standard deviation [SD]) central macular thickness (CMT) at the enrolment and last visit was 302.2 (58.4) and 293.3 (78.2) µm, respectively. Fluorescein angiography was pathological in 63.2% of procedures, with a mean (SD) Angiography Scoring for Uveitis Working Group (ASUWOG) of 17.9 (15.5). At the last visit, ocular damage according to the BD Overall Damage Index (BODI) was documented in 73.3% of eyes. The final mean (SD) best corrected visual acuity (BCVA) logMAR was 0.17 (0.47) and blindness (BCVA logMAR < 1.00 or central visual field ≤ 10°) occurred in 15.6% of eyes. At multivariate regression analysis, human leukocyte antigen (HLA)-B51 + independently predicted a + 0.35 change in the final BCVA logMAR (p = 0.01), while a higher BCVA logMAR at the first assessment (odds ratio [OR] 5.80; p = 0.02) independently predicted blindness. CONCLUSIONS: The results of this study may be leveraged to guide clinical practice and future research on this rare sight-threatening condition.
RESUMEN
PURPOSE: The clinical relevance of human leukocyte antigen (HLA) subtypes such as HLA-B51 on Behçet's disease (BD)-related uveitis and non-infectious uveitis (NIU) unrelated to BD remains largely unknown. METHODS: Data were prospectively collected from the International AIDA Network Registry for BD and for NIU. We assessed differences between groups (NIU unrelated to BD and positive for HLA-B51, BD-related uveitis positive for HLA-B51 and BD-related uveitis negative for HLA-B51) in terms of long-term ocular complications, visual acuity (VA) measured by best corrected visual acuity (BCVA), anatomical pattern, occurrence of retinal vasculitis (RV) and macular edema over time. RESULTS: Records of 213 patients (341 eyes) were analyzed. No differences in complications were observed (p = 0.465). With regard to VA, a significant difference was detected in median BCVA (p = 0.046), which was not maintained after Bonferroni correction (p = 0.060). RV was significantly more prevalent in NIU-affected patients who tested positive for HLA-B51, irrespective of the systemic diagnosis of BD (p = 0.025). No differences emerged in the occurrence of macular edema (p = 0.99). CONCLUSIONS: Patients with NIU testing positive for HLA-B51 exhibit an increased likelihood of RV throughout disease course, irrespective of a systemic diagnosis of BD. The rate of complications as well as VA are comparable between NIU cases unrelated to BD testing positive for HLA-B51 and uveitis associated with BD. Therefore, it is advisable to perform the HLA-B typing in patients with NIU or retinal vasculitis, even in the absence of typical BD features.