RESUMO
BACKGROUND: Diurnal variations in foveal thickness have been reported in several ocular pathologies including X-linked retinoschisis (XLRS), but its underlying mechanism is poorly understood. Rods are active under scotopic conditions with high metabolic demand, and its decrease may have positive effect on metabolic activity and macular thickness. The purpose of this study is to evaluate whether exposure to light and diurnal variation influence macular thickness in XLRS patients. METHODS: Five patients with clinical suspicion of XLRS underwent RS1 gene sequencing and optical coherence tomography measurements at three consecutive times: morning following sleep in a dark room, morning following sleep in an illuminated room, and late afternoon following sleep in an illuminated room. Central macular thickness (CMT) was compared between measurements, and molecular analysis was performed. RESULTS: Five RS1 mutations were identified: p.Gly140Arg, p.Arg141Cys, p.Gly109Glu, p.Pro193Leu, and p.Arg200His in patients 1-5, respectively. Two patients (4-5) had atrophied macula and were excluded from macular thickness variation analysis. A significant decrease in CMT between morning and afternoon measurements was observed in all patients (1-3: mean: 455.0 ± 32 µm to 342.17 ± 39 µm, 25%). Morning measurements following sleep in an illuminated room show a CMT reduction in all eyes of all patients with a mean reduction of 113 µm (mean: 547.17 ± 105 µm to 455.0 ± 32 µm, 17%). CONCLUSIONS: Among XLRS patients, CMT decreased at the afternoon compared to the morning of the same day and may be reduced following sleep in an illuminated room. These results help shed light on the pathophysiologic process underlying intraretinal fluid accumulation involved with the disease.
Assuntos
Ritmo Circadiano/fisiologia , Eletrorretinografia/métodos , Proteínas do Olho/genética , Macula Lutea/patologia , Retinosquise/diagnóstico , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adulto , DNA/genética , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Retinosquise/genética , Retinosquise/metabolismo , Adulto JovemRESUMO
PURPOSE: This study reports the presentation of 2 families with macular corneal dystrophy (MCD). The aim of this study was to show whether ultrasound biomicroscopy (UBM) can, based on posterior changes of the cornea in MCD, assist in the choice of surgery, either anterior lamellar keratoplasty (DALK) or penetrating keratoplasty (PK), compared with optical coherence tomography (OCT) and Scheimpflug. METHODS: Six patients with MCD were examined for their best-corrected visual acuity, slit-lamp, OCT, UBM, and Scheimpflug findings. Blood samples for DNA and exons of the CHST6 gene were screened for mutations. RESULTS: All 6 patients showed typical MCD signs at the slit lamp. Corneal transplantation was required in 2 patients in both eyes. Recurrence of MCD was observed in 2 eyes after the DALK procedure (patient A5, age 48 years, right eye and B1, 51 years, left eye), whereas the 2 eyes after PK (patient A5, age 48 years, left eye and patient B1, 51 years, right eye) remained clear (for 10 years of follow-up in patient A5 and 4 years in patient B1). In 2 patients (A1 and A3), corneal thinning could be evaluated by OCT. In 3 patients (A2, 3, and 4), UBM disclosed deeper pathologies including opacities, loss of continuity, and focal protrusions of the posterior cornea, which were not evident by other devices. In family A, a novel mutation was identified. CONCLUSIONS: Our UBM examination of MCD shows alterations of the cornea's posterior layer and confirms the known clinical and histological findings of MCD that PK represents the therapy of choice, contrary to DALK. The novel CHST6 mutation shows the heterogeneity of MCD.
Assuntos
Distrofias Hereditárias da Córnea/diagnóstico , Transplante de Córnea , Endotélio Corneano/patologia , Ceratoplastia Penetrante , Adolescente , Distrofias Hereditárias da Córnea/genética , Distrofias Hereditárias da Córnea/cirurgia , Análise Mutacional de DNA , Seguimentos , Humanos , Microscopia Acústica , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Recidiva , Sulfotransferases/genética , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Adulto Jovem , Carboidrato SulfotransferasesRESUMO
OBJECTIVE: To explore the safety and efficacy of CF101, an A(3) adenosine receptor agonist, in patients with moderate to severe dry eye syndrome. DESIGN: Phase 2, multicenter, randomized, double-masked, placebo-controlled, parallel-group study. PARTICIPANTS: Sixty-eight patients completed the study, 35 patients in the placebo group and 33 patients in the CF101 group. INTERVENTION: Patients were treated orally with either 1 mg CF101 pills or matching vehicle-filled placebo pills, given twice daily for 12 weeks, followed by a 2-week posttreatment observation. MAIN OUTCOME MEASURES: An improvement of more than 25% over baseline at week 12 in one of the following parameters: (1) tear break-up time (BUT); (2) superficial punctate keratitis assessed by fluorescein staining results; and (3) Schirmer tear test 1 results. Clinical laboratory safety tests, ophthalmic examinations, intraocular pressure (IOP) measurements, electrocardiographic evaluations, vital sign measurements, and monitoring of adverse events. RESULTS: A statistically significant increase in the proportion of patients who achieved more than 25% improvement in the corneal staining and in the clearance of corneal staining was noted between the CF101-treated group and the placebo group. Treatment with CF101 resulted in a statistically significant improvement in the mean change from baseline at week 12 of the corneal staining, BUT, and tear meniscus (TM) height in the CF101-treated group. CF101 was well tolerated and exhibited an excellent safety profile with no serious adverse events. A statistically significant decrease from baseline was observed in the IOP of the CF101-treated group in comparison with the placebo group. CONCLUSIONS: CF101, given orally, induced a statistically significant improvement in the corneal staining and an improvement in the BUT and TM in patients with moderate to severe dry eye syndrome. The drug was very well tolerated. These data and the anti-inflammatory characteristic of CF101 support further study of the drug as a potential treatment for the signs and symptoms of dry eye syndrome. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.