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PURPOSE: Comparing the effect of half-dose photodynamic therapy and high-density subthreshold micropulse laser treatment on retinal pigment epithelial detachments (PEDs) in chronic central serous chorioretinopathy. METHODS: This study included data from the PLACE trial, a prospective randomized controlled trial comparing half-dose photodynamic therapy and high-density subthreshold micropulse laser treatment in chronic central serous chorioretinopathy. Main outcome measurements were changes in both the foveal PED and the highest PED within the macula at baseline compared with first and final evaluation visit. RESULTS: At baseline, a macular PED was detected in 76.9% of patients (123/160), and a PED within 1,500 µm from the foveal center in 37.5% of patients (60/160). In the half-dose photodynamic therapy arm (61 patients), there was a significantly larger decrease in the highest macular PED compared with the high-density subthreshold micropulse laser treatment arm (62 patients) at both first and final evaluation visits (P < 0.001 and P = 0.012, respectively). The decrease of highest foveal PED was significant at first visit (P = 0.025). CONCLUSION: Half-dose photodynamic therapy is superior to high-density subthreshold micropulse laser treatment with regard to a statistically significant reduction in the height of macular PEDs in active chronic central serous chorioretinopathy. These findings may also have implications for other diseases within the pachychoroid disease spectrum that can present with PEDs.
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Coriorretinopatía Serosa Central , Terapia por Láser , Fotoquimioterapia , Desprendimiento de Retina , Coriorretinopatía Serosa Central/complicaciones , Coriorretinopatía Serosa Central/diagnóstico , Coriorretinopatía Serosa Central/terapia , Enfermedad Crónica , Angiografía con Fluoresceína , Humanos , Rayos Láser , Fármacos Fotosensibilizantes/uso terapéutico , Estudios Prospectivos , Desprendimiento de Retina/complicaciones , Desprendimiento de Retina/diagnóstico , Tomografía de Coherencia Óptica , Agudeza VisualRESUMEN
PURPOSE: To compare the effects of half-dose photodynamic therapy (PDT) and high-density subthreshold micropulse laser on choroidal dysfunction evaluated by degree and extent of hyperfluorescence on indocyanine green angiography (ICGA) in chronic central serous chorioretinopathy. METHODS: Data from the multicenter, randomized, controlled PLACE trial were used in this study. Hyperfluorescent and hypofluorescent areas on ICGA, their association with subretinal fluid and visual function were assessed. RESULTS: In total, 146 patients were included (72 in the PDT and 74 in the high-density subthreshold micropulse laser treatment arm). A significantly greater decrease in the size of hyperfluorescent areas on ICGA at first visit after treatment was seen after PDT compared with high-density subthreshold micropulse laser (mean, -1.41 ± 2.40 mm2 vs. -0.04 ± 0.73 mm2, respectively; P < 0.001). A reduction in the degree of hyperfluorescence on ICGA decreased the odds of having persistent subretinal fluid on optical coherence tomography at first visit after treatment (B = 0.295; P = 0.019). There were no significant differences in best-corrected visual acuity and retinal sensitivity between the subgroup with novel hypofluorescence (n = 20, 28%) on ICGA at first visit post PDT, compared with the subgroup without novel hypofluorescence on ICGA after PDT. CONCLUSION: Choroidal abnormalities in chronic central serous chorioretinopathy can be effectively treated by ICGA-guided half-dose PDT but not with high-density subthreshold micropulse laser application.
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Coriorretinopatía Serosa Central/terapia , Coroides/fisiopatología , Terapia por Láser , Fotoquimioterapia , Adulto , Coriorretinopatía Serosa Central/tratamiento farmacológico , Coriorretinopatía Serosa Central/fisiopatología , Coriorretinopatía Serosa Central/cirugía , Coroides/diagnóstico por imagen , Enfermedad Crónica , Colorantes/administración & dosificación , Femenino , Angiografía con Fluoresceína , Humanos , Verde de Indocianina/administración & dosificación , Masculino , Persona de Mediana Edad , Fármacos Fotosensibilizantes/uso terapéutico , Estudios Prospectivos , Retina/fisiopatología , Líquido Subretiniano , Tomografía de Coherencia Óptica , Verteporfina/uso terapéutico , Agudeza Visual/fisiologíaRESUMEN
PURPOSE: To describe the treatment outcomes and recurrence risk of chronic central serous chorioretinopathy (cCSC) in patients who had complete resolution of subretinal fluid (SRF) after either primary half-dose photodynamic therapy (PDT) or high-density subthreshold micropulse laser (HSML) in the PLACE trial. METHODS: This multicentre prospective follow-up study evaluated cCSC patients at 1 year after completion of the PLACE trial. Outcomes included: complete resolution of SRF on OCT, best-corrected visual acuity (BCVA) in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, retinal sensitivity on microperimetry and a visual function questionnaire (NEI-VFQ25). RESULTS: Twenty-nine out of 37 patients who received half-dose PDT and 15 out of 17 patients who received HSML could be evaluated at final visit. At final visit, 93% of the patients treated with half-dose PDT had complete resolution of SRF, compared with 53% of HSML-treated patients (p = 0.006). At final visit, the mean estimate increase in the PDT group compared with the HSML group was + 2.1 ETDRS letters, +0.15 dB for the retinal sensitivity and + 5.1 NEI-VFQ25 points (p = 0.103, p = 0.784 and p = 0.071, respectively). The mean estimated central retinal thickness in the half-dose PDT group was -7.0 µm compared with the HSML group (p = 0.566). The mean estimated subfoveal choroidal thickness in the half-dose PDT group was -16.6 µm compared with the HSML group (p = 0.359). CONCLUSION: At 20 months after treatment, cCSC patients successfully treated with half-dose PDT are less likely to have recurrences of SRF compared with those successfully treated with HSML. However, functional outcomes did not differ.
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Coriorretinopatía Serosa Central/tratamiento farmacológico , Coroides/diagnóstico por imagen , Terapia por Láser/métodos , Fotoquimioterapia/métodos , Retina/diagnóstico por imagen , Verteporfina/uso terapéutico , Agudeza Visual , Coriorretinopatía Serosa Central/diagnóstico , Femenino , Angiografía con Fluoresceína/métodos , Estudios de Seguimiento , Fondo de Ojo , Humanos , Masculino , Persona de Mediana Edad , Fármacos Fotosensibilizantes/uso terapéutico , Estudios Prospectivos , Factores de Tiempo , Tomografía de Coherencia Óptica/métodos , Resultado del TratamientoRESUMEN
PURPOSE: To report the long-term follow-up (12 years) of a 36-year-old male patient with crystalline keratopathy of both eyes, diagnosed with monoclonal gammopathy of undetermined significance (MGUS). Complete ophthalmic, systemic, and corneal immunohistochemical evaluations were performed. OBSERVATIONS: Slit-lamp examination revealed bilateral fine iridescent confluent crystalline deposits in all layers of the cornea, both peripherally and centrally. Systemic evaluation revealed abnormal M protein, IgG-kappa type, in blood and urine. Bone marrow aspiration showed a monoclonal plasma cell concentration of 2%. Consequently, the patient was diagnosed with MGUS. Because of progressive bilateral visual loss in the following 10 years, a perforating keratoplasty was performed on the left eye. Immunohistochemical analysis of the native cornea (the corneal button) revealed depositions of the same M protein type as detected in plasma and urine. Electron microscopy showed rhomboid-shaped corneal deposits of various sizes up to 4 µm. Recurrence of crystalline keratopathy was observed 9 months after keratoplasty. The monoclonal protein remained stable and the MGUS did not progress to multiple myeloma nor a related disorder. CONCLUSIONS AND IMPORTANCE: Crystalline keratopathy may be associated with MGUS in otherwise healthy individuals. If the keratopathy causes binocular visual loss, a corneal transplantation may be required. Unfortunately, recurrence of crystalline deposits in the corneal graft may occur within one year. This suggests that patients with vision impairment due to paraproteinemic keratopathy who are diagnosed as MGUS, in fact, have a monoclonal gammopathy of ocular significance (MGOS).
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PURPOSE: To assess whether chronic central serous chorioretinopathy (cCSC) patients without a complete resolution of subretinal fluid (SRF) after either half-dose photodynamic therapy (PDT) or high-density subthreshold micropulse laser (HSML) treatment may benefit from crossover treatment. DESIGN: Multicenter prospective interventional case series. METHODS: cCSC patients with persistent SRF at the final visit of the PLACE trial were included. Patients received crossover treatment with either half-dose PDT or HSML. RESULTS: Thirty-two patients received PDT and 10 patients received HSML. At the first evaluation visit (6-8 weeks after treatment), 81% of patients in the PDT group had complete resolution of SRF, while none of the HSML-treated patients had complete resolution of SRF. At final visit (1 year after baseline), 78% (P = .030) and 67% (P = .109) of the patients, respectively, had a complete resolution of SRF. The mean retinal sensitivity in the PDT group increased from 21.7 dB (standard error [SE]: 0.9) to 23.4 dB (SE: 0.8) at evaluation visit 1 (P = .003), to 24.7dB (SE: 0.8) at final visit (P < .001), while there were no significant changes in the HSML group (23.7 dB [SE: 1.6] at baseline, 23.8 dB [SE: 1.4] at evaluation 1, and 23.3 dB [SE: 1.4] at final visit). The mean visual acuity and mean visual quality-of-life questionnaire score did not change significantly in both groups. CONCLUSIONS: Crossover to half-dose PDT after previous unsuccessful HSML treatment for cCSC may lead to improved anatomic and functional endpoints, while crossover to HSML after half-dose PDT does not seem to significantly affect these endpoints.
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Coriorretinopatía Serosa Central/terapia , Fotocoagulación/métodos , Fotoquimioterapia/métodos , Agudeza Visual/fisiología , Adulto , Coriorretinopatía Serosa Central/tratamiento farmacológico , Coriorretinopatía Serosa Central/fisiopatología , Coriorretinopatía Serosa Central/cirugía , Enfermedad Crónica , Colorantes/administración & dosificación , Estudios Cruzados , Método Doble Ciego , Femenino , Angiografía con Fluoresceína , Humanos , Verde de Indocianina/administración & dosificación , Láseres de Semiconductores/uso terapéutico , Masculino , Persona de Mediana Edad , Fármacos Fotosensibilizantes/uso terapéutico , Estudios Prospectivos , Calidad de Vida/psicología , Perfil de Impacto de Enfermedad , Líquido Subretiniano , Encuestas y Cuestionarios , Tomografía de Coherencia Óptica , Insuficiencia del TratamientoRESUMEN
Chronic central serous chorioretinopathy (cCSC) is a multifactorial eye disease characterized by subretinal fluid accumulation that leads to vision loss. Clinically, cCSC is associated with stress, hypercortisolism and corticosteroid use, and is more frequent in males (80%) than in females (20%). Current genetic studies on cCSC have thus far focussed on common variants, but familial occurrence of cCSC also suggests a role for rare variants in the disease susceptibility. Therefore, in this study, we performed exome sequencing of cCSC patients to elucidate the role of rare (protein-altering) variants in the disease. Exome sequencing was performed on 269 cCSC patients and 1,586 controls. Data were processed according to the Genome-Analysis-Toolkit (GATK) best practices. Principal component analysis was performed to check for genetic ancestry and only unrelated subjects of European descent were retained. Burden, SKAT and SKAT-O tests were performed using 2 different grouping criteria. One group included protein-altering variants only, while the other contained synonymous and splice site variants as well. The gene-based analyses were performed using the SKAT R-package correcting for two principal components using two approaches; (1) on the entire cohort correcting for sex and (2) on males and females separately. Additionally, the gene-based associations of genes at previously reported cCSC loci were investigated. After filtering, the dataset contained 263 cCSC patients (208 males [79%]) and 1352 controls (671 males [50%]) carrying 197,915 protein-altering variants in 16,370 genes and 330,689 exonic variants in 18,173 genes. Analysis stratified by sex identified significant associations with the PIGZ (PSKAT = 9.19 × 10-7 & PSKAT-O = 2.48 × 10-6), DUOX1 (PSKAT = 1.03 × 10-6), RSAD1 (PSKAT = 1.92 × 10-7 & PSKAT-O = 8.57 × 10-8) and LAMB3 (PBurden = 1.40 × 10-6 & PSKAT-O = 1.14 × 10-6) genes in female cCSC patients, after correction for multiple testing. The number of rare variant carriers in these genes was significantly higher in the female cCSC cohort compared to female controls (45,5% vs. 18.5%, P = 1.92 × 10-6, OR = 3.67 [95% CI = 2.09-6.46]). No significant associations were identified in the entire cohort nor in the male patients. In this exome study on cCSC patients, we have identified PIGZ, DUOX1, RSAD1 and LAMB3 as potential new candidate genes for cCSC in females. The sex-specific associations identified here suggest a possible interaction between rare genetic factors and sex for cCSC, but replication of these findings in additional cohorts of cCSC patients is necessary.
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Coriorretinopatía Serosa Central/genética , Exoma/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Moléculas de Adhesión Celular/genética , Coriorretinopatía Serosa Central/diagnóstico por imagen , Coriorretinopatía Serosa Central/patología , Oxidasas Duales/genética , Femenino , Angiografía con Fluoresceína , Genotipo , Humanos , Masculino , Manosiltransferasas/genética , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Polimorfismo de Nucleótido Simple/genética , Proteínas/genética , Retina/diagnóstico por imagen , Retina/metabolismo , Retina/patología , Tomografía de Coherencia Óptica , Secuenciación del Exoma , KalininaRESUMEN
PURPOSE: To describe the characteristics and potential differences between focal and diffuse phenotypes of untreated chronic central serous chorioretinopathy (cCSC). METHODS: For this study, patients were divided in two groups. Focal leakage was defined as 1 "hot spot" of leakage, whereas diffuse leakage was defined as either > 1 hot spot or a larger area of widespread leakage on FA. Clinical characteristics were assessed at presentation. After Bonferroni correction, P values < 0.00125 were deemed statistically significant. RESULTS: The focal leakage group included 68 eyes (53 males), and the diffuse leakage group included 105 eyes (88 males). Mean best-corrected visual acuity (BCVA) was 77.1 ± 8.1 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters in the focal group and 76.0 ± 9.6 ETDRS letters in the diffuse group (p = 0.440). In the focal group, mean age was 46.9 ± 8.8 years, whereas this was 49.7 ± 8.3 years in the diffuse group (p = 0.033). Mean central foveal thickness was 107.1 ± 21.3 µm in the focal group and 106.2 ± 27.3 µm in the diffuse group (p = 0.818). Mean choroidal thickness was 407.5 ± 114.8 µm in the focal group and 419.1 ± 113.9 µm in the diffuse group (p = 0.578). In the focal group, subretinal fluid was present in the fellow eye in 16% of the patients, as compared to 29% in the diffuse group (p = 0.067). CONCLUSIONS: In untreated cCSC patients with focal or diffuse leakage on FA, no marked differences in clinical characteristics were found. Extensive choroidal abnormalities may be present in both groups, which are presumed to lie at the basis of the development of cCSC.
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Coriorretinopatía Serosa Central/diagnóstico , Coroides/patología , Angiografía con Fluoresceína/métodos , Retina/patología , Líquido Subretiniano/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Coriorretinopatía Serosa Central/fisiopatología , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Fondo de Ojo , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
PURPOSE: To compare the outcome between high-density subthreshold micropulse laser (HSML) treatment and half-dose photodynamic therapy (PDT) in chronic central serous chorioretinopathy (cCSC) patients, subdivided based on either focal or diffuse leakage on fluorescein angiography (FA). DESIGN: Retrospective analysis of multicenter randomized controlled trial data. METHODS: Patients were treated with either half-dose PDT or HSML (both indocyanine green angiography-guided) and categorized in 2 groups, based on focal or diffuse leakage on FA. Clinical outcomes were evaluated at baseline and during follow-up. RESULTS: In the focal leakage group (63 patients), both at first evaluation and at final visit, more PDT-treated than HSML-treated patients demonstrated a resolution of subretinal fluid (evaluation visit 1: 57% in the PDT group and 17% in the HSML group, P = .007; final visit: 75% and 38%, P = .012). In the diffuse leakage group (93 patients), both at first evaluation and at final visit, more PDT-treated than HSML-treated patients showed a resolution of subretinal fluid (evaluation visit: 1:48% in the PDT group and 16% in the HSML group, P = .002; final visit: 67% and 21%, P = .002). PDT-treated patients in the focal and diffuse leakage group had a higher retinal sensitivity increase, comparing baseline and final visit (+3.1 ± 3.1 dB vs +1.2 ± 4.0 dB, P = .048, and +2.7 ± 3.3 dB vs +1.0 ± 3.8 dB, P = .036, respectively). Only in the diffuse leakage group, the increase in ETDRS letters was higher in the PDT-treated group when comparing baseline and first evaluation visit (+4.4 ± 6.1 vs +0.9 ± 10.0, P = .049). CONCLUSIONS: Half-dose PDT is superior to HSML treatment in cCSC patients, regardless of the presence of focal or diffuse leakage on FA.
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Coriorretinopatía Serosa Central/tratamiento farmacológico , Coroides/patología , Rayos Láser , Fotoquimioterapia/métodos , Retina/patología , Verteporfina/uso terapéutico , Agudeza Visual , Coriorretinopatía Serosa Central/diagnóstico , Enfermedad Crónica , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Fondo de Ojo , Humanos , Masculino , Persona de Mediana Edad , Fármacos Fotosensibilizantes/uso terapéutico , Estudios Retrospectivos , Factores de Tiempo , Tomografía de Coherencia Óptica , Resultado del TratamientoRESUMEN
BACKGROUND: Central serous chorioretinopathy (CSC) is a chorioretinal disease characterized by fluid accumulation between the neuroretina and retinal pigment epithelium with unknown etiology. Family studies have suggested a heritable component for CSC with an autosomal dominant inheritance pattern. Therefore, exome sequencing was performed on familial cCSC to indentify the genetic components contributing to familial cCSC. METHODS: Exome sequencing was performed on 72 individuals of 18 families with CSC. In these families, we determined whether rare genetic variants (minor allele frequency < 1%) were segregated with CSC and also performed familial gene-burden analysis. RESULTS: In total, 11 variants segregated in two out of 18 families. One of these variants, c.4145C>T; p.T1382I (rs61758735) in the PTPRB gene, was also associated with CSC in a large case-control cohort sequenced previously (p = 0.009). Additionally, in 28 genes two or more different heterozygous variants segregated in two or more families, but no gene showed consistent associations in both the family gene-burden results and gene-burden analysis in the case-control cohort. CONCLUSION: We identified potential candidate genes for familial CSC and managed to exclude Mendelian inheritance of variants in one or a limited number of genes. Instead, familial CSC may be a heterogeneous Mendelian disease caused by variants in many different genes, or alternatively CSC may represent a complex disease to which both environmental factors and genetics contribute.
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Coriorretinopatía Serosa Central/genética , Frecuencia de los Genes , Femenino , Humanos , Masculino , Linaje , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/genética , Secuenciación del ExomaRESUMEN
PURPOSE: To assess ophthalmologic characteristics in patients and unaffected individuals in families with multiple members affected by central serous chorioretinopathy (CSC), both at presentation and long-term follow-up. METHODS: In 103 subjects from 23 families with at least 2 affected patients with CSC per family, prospective extensive ophthalmologic examination was performed, including best-corrected visual acuity, indirect ophthalmoscopy, digital color fundus photography, optical coherence tomography, fundus autofluorescence, and fluorescein angiography imaging. From these, 24 individuals from 6 families had undergone extensive ophthalmologic examination in either 1994 or 1995 and were followed up in this study. RESULTS: Subretinal fluid accumulation on optical coherence tomography and/or "hot spots" of leakage on fluorescein angiography indicative of CSC were detected in 45 of 103 phenotyped subjects (44%). Findings suggestive of CSC, but without the presence of subretinal fluid on optical coherence tomography and/or "hot spots" of leakage on fluorescein angiography, were observed in an additional 27 family members (26%). In 4 of 17 previously nonaffected subjects (24%) from the 24 individuals that were followed up after more than 20 years, we found more severe abnormalities. CONCLUSION: Extensive ophthalmologic phenotyping resulted in the detection of (suggestive) CSC in 52% of family members of patients with CSC. Genetic factors may play an important role in these specific CSC cases. Moreover, during follow-up, progressive disease can occur in a noteworthy number of patients.
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Coriorretinopatía Serosa Central/genética , Coroides/patología , Angiografía con Fluoresceína/métodos , Oftalmoscopía/métodos , Retina/patología , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Coriorretinopatía Serosa Central/diagnóstico , Coriorretinopatía Serosa Central/epidemiología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Fondo de Ojo , Humanos , Incidencia , Masculino , Países Bajos/epidemiología , Linaje , Fenotipo , Estudios ProspectivosRESUMEN
PURPOSE: To describe a spectrum of severe chronic central serous chorioretinopathy (cCSC) cases and their response to photodynamic therapy (PDT). PATIENTS AND METHODS: A total of 66 patients (81 eyes) with active severe cCSC were studied, and their response to PDT was compared with a control group consisting of 35 active cCSCs (37 eyes) that did not display characteristics of severity. Best-corrected visual acuity (BCVA) and complete resolution of subretinal fluid (SRF) were considered as main outcome measures. RESULTS: In severe cCSC cases, we found cumulative areas of diffuse atrophic retinal pigment epithelium alterations in 48 eyes (59%), multiple "hot spots" of leakage in 36 eyes (44%), posterior cystoid retinal degeneration in 25 eyes (31%), and 13 eyes (16%) had a diffuse leakage on fluorescein angiography. After PDT treatment, BCVA increased in both groups, from 66 to 72 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters in the case group (P<0.001), and from 78 to 82 ETDRS letters in the control group (P<0.001). SRF had resolved completely in 87% of severe cCSC cases and 95% of controls at final follow-up visit. CONCLUSION: A spectrum of severe cCSC exists, and PDT seems to be an effective treatment in both severe cCSC and nonsevere cCSC in terms of resolution of SRF. Final BCVA shows a significant improvement in both groups after PDT treatment.
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Importance: To date, several targeted genetic studies on chronic central serous chorioretinopathy (cCSC) have been performed; however, unbiased genome-wide studies into the genetics of cCSC have not been reported. To discover new genetic loci associated with cCSC and to better understand the causative mechanism of this disease, we performed a genome-wide association study (GWAS) on patients with cCSC. Objective: To discover new genetic loci and pathways associated with cCSC and to predict the association of genetic variants with gene expression in patients with cCSC. Design, Setting, and Participants: This case-control GWAS was completed in the general community, 3 referral university medical centers, and outpatient care on Europeans individuals with cCSC and population-based control participants. Genotype data was collected from May 2013 to August 2017, and data analysis occurred from August 2017 to November 2017. Main Outcomes and Measures: Associations of single-nucleotide polymorphisms, haplotypes, genetic pathways, and predicted gene expression with cCSC. Results: A total of 521 patients with cCSC (median age, 51 years; interquartile range [IQR], 44-59 years; 420 [80.6%] male) and 3577 European population-based control participants (median age, 52 years; IQR, 37-71 years; 1630 [45.6%] male) were included. One locus on chromosome 1 at the complement factor H (CFH) gene reached genome-wide significance and was associated with an increased risk of cCSC (rs1329428; odds ratio [OR], 1.57 [95% CI, 1.38-1.80]; P = 3.12 × 10-11). The CFH haplotypes H1 and H3 were protective for cCSC (H1: OR, 0.64 [95% CI, 0.53-0.77]; P = 2.18 × 10-6; H3: OR, 0.54 [95% CI, 0.42-0.70]; P = 2.49 × 10-6), whereas haplotypes H2, H4, H5, and the aggregate of rare CFH haplotypes conferred increased risk (H2: OR, 1.57 [95% CI, 1.30-1.89]; P = 2.18 × 10-6; H4: OR, 1.43 [95% CI, 1.13-1.80]; P = 2.49 × 10-3; H5: OR, 1.80 [95% CI, 1.36-2.39]; P = 4.61 × 10-5; rare haplotypes: OR, 1.99 [95% CI, 1.43-2.77]; P = 4.59 × 10-5). Pathway analyses showed involvement of the complement cascade and alternative open reading frame (ARF) pathway in cCSC. Using PrediXcan, we identified changes in predicted expression of complement genes CFH, complement factor H related 1 (CFHR1), complement factor related 4 (CFHR4), and membrane cofactor protein (MCP/CD46). Additionally, the potassium sodium-activated channel subfamily T member 2 (KCNT2) and tumor necrosis factor receptor superfamily member 10a (TNFRSF10A) genes were differentially expressed in patients with cCSC. Conclusions and Relevance: In this GWAS on cCSC, we identified a locus on chromosome 1 at the CFH gene that was significantly associated with cCSC, and we report protective and risk-conferring haplotypes in this gene. Pathway analyses were enriched for complement genes, and gene expression analysis suggests a role for CFH, CFHR1, CFHR4, CD46, KCNT2, and TNFRSF10A in the disease. Taken together, these results underscore the potential importance of the complement pathway in the causative mechanisms of cCSC.
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Coriorretinopatía Serosa Central/genética , Cromosomas Humanos Par 1/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Estudios de Casos y Controles , Coriorretinopatía Serosa Central/diagnóstico , Enfermedad Crónica , Factor H de Complemento/genética , Femenino , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Población Blanca/genéticaRESUMEN
PURPOSE: To compare the anatomic and functional efficacy and safety of half-dose photodynamic therapy (PDT) versus high-density subthreshold micropulse laser (HSML) treatment in patients with chronic central serous chorioretinopathy (cCSC). DESIGN: Open-label, multicenter, randomized controlled clinical trial. PARTICIPANTS: Patients with cCSC whose disease had to be confirmed by both clinical characteristics and findings on multimodal imaging. METHODS: Eligible patients were randomized in a 1:1 allocation ratio. Treatment was evaluated during a follow-up visit, and the same treatment was repeated in patients who still demonstrated subretinal fluid (SRF). MAIN OUTCOME MEASURES: The primary end point was the complete disappearance of SRF at the first evaluation visit at 6 to 8 weeks after treatment. As a secondary outcome measure, we assessed this anatomic result at the final evaluation visit at 7 to 8 months after treatment. Other secondary outcomes covered functional improvement and included change in best-corrected visual acuity (BCVA; measured in Early Treatment Diabetic Retinopathy Study [ETDRS] letters), retinal sensitivity (measured using microperimetry), and vision-related quality of life using a validated questionnaire. RESULTS: Between November 2013 and September 2016, 179 patients were included: 89 patients were assigned randomly to half-dose PDT, and 90 were assigned randomly to HSML treatment. At their first evaluation visit, SRF had resolved in 51.2% and 13.8% of patients, respectively (P < 0.001). At their final evaluation visit, a significantly higher percentage of PDT-treated patients demonstrated no SRF (67.2% vs. 28.8%; P < 0.001). Moreover, at the first evaluation visit, the PDT-treated patients showed a significantly higher increase in BCVA (+4.60±6.62 ETDRS letters vs. +1.39±8.99 ETDRS letters; P = 0.011), and a significantly higher increase in retinal sensitivity on microperimetry (+2.01±3.04 dB vs. +0.92±3.65 dB; P = 0.046); however, the improvement in vision-related quality of life was similar (score of +2.87±8.35 vs. +2.56±7.36, respectively; P = 0.800). CONCLUSIONS: Half-dose PDT is superior to HSML for treating cCSC, leading to a significantly higher proportion of patients with complete resolution of SRF and functional improvement.
Asunto(s)
Coriorretinopatía Serosa Central/terapia , Terapia por Láser/métodos , Imagen Multimodal/métodos , Fotoquimioterapia/métodos , Verteporfina/administración & dosificación , Agudeza Visual , Coriorretinopatía Serosa Central/diagnóstico , Coriorretinopatía Serosa Central/fisiopatología , Coroides/patología , Relación Dosis-Respuesta a Droga , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Fondo de Ojo , Humanos , Masculino , Persona de Mediana Edad , Oftalmoscopía , Fármacos Fotosensibilizantes/administración & dosificación , Epitelio Pigmentado de la Retina/patología , Tomografía de Coherencia Óptica , Resultado del TratamientoRESUMEN
Importance: Chronic central serous chorioretinopathy (cCSC) is a chorioretinal disease with unknown disease etiology. The glucocorticoid receptor and the mineralocorticoid receptor, 2 glucocorticoid-binding receptors, might be involved in the pathogenesis of cCSC. Objective: To assess the association of functional variants and haplotypes in the glucocorticoid receptor (NR3C1) and mineralocorticoid receptor (NR3C2) genes with cCSC. Design, Setting, and Participants: In this case-control genetic association study, 336 patients with cCSC and 1314 unaffected controls, collected at 3 university medical centers from September 1, 2009, to May 1, 2016, underwent KASP genotyping for selected variants in NR3C1 (rs56149945, rs41423247, and rs6198) and NR3C2 (rs2070951 and rs5522). Main Outcomes and Measures: Genetic associations of 3 NR3C1 variants and 2 NR3C2 variants with cCSC. Results: Among the 336 patients (274 men and 62 women; mean [SD] age, 52 [10] years), after correction for multiple testing, rs2070951 in the NR3C2 gene was significantly associated with cCSC (odds ratio, 1.29; 95% CI, 1.08-1.53; P = .004). Moreover, the GA haplotype of single-nucleotide polymorphisms rs2070951 and rs5522 in NR3C2 conferred risk for cCSC (odds ratio, 1.39; 95% CI, 1.15-1.68; P = .004), whereas the CA haplotype decreased risk for cCSC (odds ratio, 0.72; 95% CI, 0.60-0.87; P < .001). Three known variants in NR3C1 that alter the activity of the glucocorticoid receptor (rs56149945, rs41423247, and rs6198) were not associated with cCSC. Conclusions and Relevance: In this study, the variant rs2070951 and the GA haplotype in NR3C2 were associated with an increased risk for cCSC. Results of this genetic study support a possible role for the mineralocorticoid receptor in the pathogenesis of cCSC. Since these haplotypes have previously been associated with perceived stress, this study provides a clue to bridging clinical risk factors for cCSC to underlying genetic associations.
Asunto(s)
Coriorretinopatía Serosa Central/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Receptores de Mineralocorticoides/genética , Coriorretinopatía Serosa Central/diagnóstico , Coriorretinopatía Serosa Central/metabolismo , Enfermedad Crónica , Femenino , Angiografía con Fluoresceína , Fondo de Ojo , Estudios de Asociación Genética , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Receptores de Mineralocorticoides/metabolismo , Estudios Retrospectivos , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: To describe the clinical findings and long-term outcome of patients with chronic central serous chorioretinopathy (cCSC). MATERIALS AND METHODS: This was a retrospective case series in 52 eyes of 36 patients with a follow-up period of at least 1 year. Extensive ophthalmic examination and a validated questionnaire concerning vision-related quality of life (National Eye Institute Visual Function Questionnaire [NEI-VFQ]-39) were analyzed. RESULTS: Mean visual acuity showed a significant decline over time of 0.16 logarithm of minimum angle of resolution ([logMAR] range: -0.22 to 1.3; P=0.009) after a mean follow-up period of 10.6 years. Also, patients reported lower vision-related quality of life based on the NEI-VFQ-39 for almost all categories compared to healthy controls. Macular atrophy was diagnosed more often on optical coherence tomography compared to other diagnostic entities. Retinal pigment epithelium detachments in the macula were documented on optical coherence tomography in 56% of the patients. A significant thinning of foveal thickness was measured over time compared to unaffected fellow eyes (P=0.002). On long-term follow-up, 13 eyes (37%) showed an increase in number of hot spots on fluorescein angiography. CONCLUSION: This study indicates that cCSC is a progressive disease in many patients, causing a progressive decline in visual acuity, accompanied by lower reported vision-related quality of life. In deciding whether or not to treat, the progressive nature of cCSC should be taken into account in this relatively young and often still professionally active patient group.
RESUMEN
PURPOSE: To investigate whether patients who developed chronic central serous chorioretinopathy (cCSC) in association with corticosteroid treatment respond differently to photodynamic therapy (PDT) as compared to patients who have not used corticosteroids. METHODS: Clinical evaluation included visual acuity (VA), fundoscopy, optical coherence tomography (OCT), fluorescein and indocyanine green angiography. The main outcome measure was a complete resolution of subretinal fluid (SRF) on OCT after PDT. RESULTS: One hundred and twenty-three eyes (117 patients), including 35 steroid-associated cases (29%), who received PDT treatment with reduced settings for active cCSC were included. Complete resolution of SRF on OCT was seen in 69% of the steroid-associated cases and in 50% of the controls after PDT treatment (p = 0.062). At the final follow-up moment, 74% of the cases had a complete resolution of SRF compared to 60% in the control group (p = 0.142). The VA at the first visit after therapy showed an increase in both groups (mean VA before treatment; cases: 69 ± 14 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, controls: 74 ± 13 ETDRS letters, mean VA first visit after treatment; cases: 76 ± 13 ETDRS letters, controls: 75 ± 13 ETDRS letters). No significant differences were seen in response to PDT between the patients who continued corticosteroid treatment and those who ceased the use of corticosteroids. CONCLUSIONS: Photodynamic therapy appears to be equally effective in patients suffering from steroid-associated cCSC as compared to patients with cCSC who do not use corticosteroids. Continuation of corticosteroids at the time of PDT treatment does not seem to adversely affect PDT response.