Effect of acute and chronic aldosterone exposure on the retinal pigment epithelium-choroid complex in rodents.

Preclinical and clinical evidences show that aldosterone and/or mineralocorticoid receptor (MR) over-activation by glucocorticoids can be deleterious to the retina and to the retinal pigment epithelium (RPE)-choroid complex. However, the exact molecular mechanisms driving these effects remain poorly understood and pathological consequences of chronic exposure of the retina and RPE/choroid to aldosterone have not been completely explored. We aimed to decipher the transcriptomic regulation in the RPE-choroid complex in rats in response to acute intraocular aldosterone injection and to explore the consequences of systemic chronic aldosterone exposure on the morphology and the gene regulation in RPE/choroid in mice. High dose of aldosterone (100 nM) was intravitreously injected in Lewis rat eyes in order to yield an aldosterone dose able to induce a molecular response at the apical side of the RPE-choroid complex. The posterior segment morphology was evaluated in vivo using optical coherence tomography (OCT) before and 24 h after aldosterone injection. Rat RPE-choroid complexes were used for RNA sequencing and analysis. Uninephrectomy/aldosterone/salt (NAS) model was created in wild-type C57BL/6 mice. After 6 weeks, histology of mouse posterior segments were observed ex vivo. Gene expression in the RPE-choroid complex was analyzed using quantitative PCR. Acute intravitreous injection of aldosterone induced posterior segment inflammation observed on OCT. RNA sequencing of rat RPE-choroid complexes revealed up-regulation of pathways involved in inflammation, oxidative stress and RNA procession, and down-regulation of genes involved in synaptic activity, muscle contraction, cytoskeleton, cell junction and transporters. Chronic aldosterone/salt exposure in NAS model induces retinal edema, choroidal vasodilation and RPE cell dysfunction and migration. Quantitative PCR showed deregulation of genes involved in inflammatory response, oxidative stress, particularly the NOX pathway, angiogenesis and cell contractility. Both rodent models share some common phenotypes and molecular regulations in the RPE-choroid complex that could contribute to pachychoroid epitheliopathy in humans. The difference in inflammatory status relies on different intraocular or systemic route of aldosterone administration and on the different doses of aldosterone exposed to the RPE-choroid complex.

Tubérculo coroideo asintomático en un paciente con enfermedad de Crohn en tratamiento con adalimumab / Asymptomatic choroidal tubercle in a patient with Crohn's disease on adalimumab treatment

Introducción: Adalimumab, un antifactor de necrosis tumoral que se utiliza en la enfermedad de Crohn activa (EC), se asocia con un mayor riesgo de tuberculosis. Caso clínico: Se describe el caso de un varón de 48 años con EC activa en tratamiento con adalimumab. Después de 3 meses desarrolló una tuberculosis pulmonar miliar, y en un estudio oftalmológico se encontró un tubérculo coroideo no reactivo solitario temporal superior al disco óptico. La angiofluoresceingrafía mostró hiperfluorescencia tardía. Con la tomografía de coherencia óptica se observó una masa plana sin desprendimiento seroso de retina. El tubérculo coroideo regresó lentamente con la terapia antituberculosa. Discusión: En pacientes con EC y en tratamiento con adalimumab, un tubérculo coroideo puede presentarse sin sintomatología vítreo-retiniana (AU)

Introduction: Adalimumab, an anti-tumour necrosis factor alpha therapy for active Crohn's disease (CD), is associated with increased risks of tuberculosis infection. Case report: The case is presented of a 48 year-old male with active CD on treatment with adalimumab. After three months, he developed a miliary pulmonary tuberculosis infection, with a solitary non-reactive choroidal tubercle temporal-superior to the optic disc being found in an ophthalmological study. Fluorescein angiography showed late hyperfluorescence in a staining pattern. Optic coherence tomography showed a flat mass without serous retinal detachment. The choroidal tubercle slowly regressed with antituberculosis therapy. Discussion: Choroidal tubercles with no vitreo-retinal symptomatology can be present in patients with CD and on treatment with adalimumab (AU)

Hiperornitinemia con atrofia gyrata de coroides y retina / Hyperornithinemia with gyrate atrophy of the choroid and retina

La atrofia gyrata de coroides y retina fue descrita por vez primera por Fuchs en el año 1896 como una entidad clínicamente definida. La deficiencia de la enzima ornitina delta aminotransferasa se hereda de forma autosómica recesiva; resulta en incremento plasmático de las concentraciones de ornitina y se asocia con atrofia gyrata de coroides y retina. Se presenta una paciente de 6 años de edad que es llevada a consulta, ya que en la escuela la maestra notaba mala visión de lejos. En un examen inicial del fondo de ojo el oftalmólogo observó cambios sugestivos de distrofia retiniana. En la oftalmoscopia binocular indirecta se encontraron extensas zonas confluentes de atrofia coroidea por fuera de las arcadas vasculares que respetaban el polo posterior; la mácula impresionaba normal. Se realizó un estudio de tomografía de coherencia óptica en dominio espectral en tomógrafo Spectralis que demostró la presencia de edema macular cistoide en ambos ojos. La determinación de niveles de ornitina en sangre arrojaron niveles muy elevados de este aminoácido (975 µmol/mL). Con todos estos hallazgos se llegó al diagnóstico de hiperornitinemia y atrofia gyrata de coroides y retina. Se indicó tratamiento dietético y vitamina B6 oral a pesar de que no se ha obtenido hasta el momento reducción significativa de los niveles de ornitina en plasma(AU)

Gyrate atrophy of the choroid and the retina was first described by Fuchs as a clinically defined condition in 1896. Human hereditary deficiency of ornithine aminotransferase activity is transmitted as an autosomal recessive trait and results in increased level of plasma ornithine and is associated with gyrate atrophy of the choroid and the retina. A 6-year-old girl was taken to the ophthalmologist's because of her far poor vision detected by her teacher at the school. In the initial eye fundus examination the ophthalmologist observed some changes indicating retinal dystrophy. The indirect binocular funduscopy revealed extensive areas of choroidal atrophy outside the vascular archades respected the posterior pole whereas the macula impressed as normal. Cystoid macular edema was evident in both eyes according to the results of the optic coherence tomography performed with Spectralis tomograph. The aminoacid analysis revealed high serum ornithine level (975 µmol/mL). The clinical diagnosis of the patient was consistent with hyper-ornithinemia and gyrate atrophy of the choroid and the retina. She was treated with vitamin B6 and dietary supplementation but no significant reduction on her serum ornithine level was observed(AU)

Hiperornitinemia con atrofia gyrata de coroides y retina / Hyperornithinemia with gyrate atrophy of the choroid and retina

La atrofia gyrata de coroides y retina fue descrita por vez primera por Fuchs en el año 1896 como una entidad clínicamente definida. La deficiencia de la enzima ornitina delta aminotransferasa se hereda de forma autosómica recesiva; resulta en incremento plasmático de las concentraciones de ornitina y se asocia con atrofia gyrata de coroides y retina. Se presenta una paciente de 6 años de edad que es llevada a consulta, ya que en la escuela la maestra notaba mala visión de lejos. En un examen inicial del fondo de ojo el oftalmólogo observó cambios sugestivos de distrofia retiniana. En la oftalmoscopia binocular indirecta se encontraron extensas zonas confluentes de atrofia coroidea por fuera de las arcadas vasculares que respetaban el polo posterior; la mácula impresionaba normal. Se realizó un estudio de tomografía de coherencia óptica en dominio espectral en tomógrafo Spectralis que demostró la presencia de edema macular cistoide en ambos ojos. La determinación de niveles de ornitina en sangre arrojaron niveles muy elevados de este aminoácido (975 µmol/mL). Con todos estos hallazgos se llegó al diagnóstico de hiperornitinemia y atrofia gyrata de coroides y retina. Se indicó tratamiento dietético y vitamina B6 oral a pesar de que no se ha obtenido hasta el momento reducción significativa de los niveles de ornitina en plasma(AU)

Gyrate atrophy of the choroid and the retina was first described by Fuchs as a clinically defined condition in 1896. Human hereditary deficiency of ornithine aminotransferase activity is transmitted as an autosomal recessive trait and results in increased level of plasma ornithine and is associated with gyrate atrophy of the choroid and the retina. A 6-year-old girl was taken to the ophthalmologist’s because of her far poor vision detected by her teacher at the school. In the initial eye fundus examination the ophthalmologist observed some changes indicating retinal dystrophy. The indirect binocular funduscopy revealed extensive areas of choroidal atrophy outside the vascular archades respected the posterior pole whereas the macula impressed as normal. Cystoid macular edema was evident in both eyes according to the results of the optic coherence tomography performed with Spectralis tomograph. The aminoacid analysis revealed high serum ornithine level (975 µmol/mL). The clinical diagnosis of the patient was consistent with hyper-ornithinemia and gyrate atrophy of the choroid and the retina. She was treated with vitamin B6 and dietary supplementation but no significant reduction on her serum ornithine level was observed(AU)

Hemangioma coroideo y terapia fotodinámica. Respuesta anatómica y funcional de los pacientes con hemangioma coroideo tratados con terapia fotodinámica / Choroidal haemangioma and photodynamic therapy. Anatomical and functional response of patients with choroidal hemangioma treated with photodynamic therapy

Objetivo: Estudiar la eficacia y las limitaciones de la terapia fotodinámica (TFD) como tratamiento de primera elección en pacientes con hemangioma coroideo circunscrito sintomático. Métodos: Se realizó un estudio retrospectivo de 16 pacientes (13 varones y 3 mujeres, con una media de edad de 54,88 años) con hemangioma coroideo circunscrito visitados en nuestro centro y tratados con TFD en los últimos 7 años. Resultados: Todos los pacientes presentaban hemangioma coroideo circunscrito, que ocasionaba sintomatología secundaria a la presencia de edema microquístico intrarretiniano o desprendimiento neurosensorial. La agudeza visual (AV) media inicial del grupo era de 0,23 y la AV media posterior a la realización de TFD fue de 0,38 (todas las AV fueron medidas en escala decimal). Cabe destacar que los pacientes necesitaron una media de 1,69 sesiones de TFD. Tres de los pacientes necesitaron un tratamiento de rescate con termoterapia transpupilar, inyección intravítrea de antifactor de crecimiento endotelial vascular (ranibizumab, aflibercept) o implante intravítreo de dexametasona (Ozurdex®). La indicación de cambio de tratamiento fue la persistencia de edema microquístico intrarretiniano y/o desprendimiento neurosensorial (o su resolución incompleta) tras 3 sesiones de TFD. Como resultados generales, destacamos que un 62,5% de los pacientes evolucionó hacia la resolución anatómica y funcional (incremento de AV o estabilidad). Conclusiones: La TFD es un procedimiento dirigido y rápido, con buena respuesta anatómica y funcional, que ocasiona un mínimo daño a los vasos adyacentes a la lesión (AU)

Objective: To study the effectiveness and limitations of photodynamic therapy (PDT) as treatment of choice in patients with symptomatic circumscribed choroidal haemangioma. Methods: A retrospective study was conducted on 16 patients (13 men and 3 women, with mean age of 54.88 years) with circumscribed choroidal haemangioma, who attended our centre and were treated with PDT in the last 7 years. Results: All patients had circumscribed choroidal haemangioma, which caused a decrease in visual acuity (VA) secondary to the presence of intraretinal microcystic oedema or neurosensory detachment. The mean initial VA was 0.23, and the final mean VA after performing PDT was 0.38 (all the VA were measured in decimal scale). It should be noted that patients needed a mean of 1.69 PDT sessions. Three of the patients needed rescue treatment with trans-pupillary thermotherapy, intravitreal injection of anti-vascular endothelial growth factor (ranibizumab, aflibercept) or a dexamethasone intravitreal implant (Ozurdex®). The indication for a change of treatment was the persistence of intraretinal microcystic oedema and/or neurosensory detachment (or incomplete resolution) after 3 PDT sessions. As overall results, 62.5% of patients evolved into anatomical and functional (increase in AV or stability) resolution. Conclusions: PDT is a straight forward and fast procedure, with a good anatomical and functional response, causing minimal damage to adjacent vessels (AU)

Idiopathic sclerochoroidal calcification.

PURPOSE: Sclerochoroidal calcification is a rare ocular condition characterized by multifocal, yellow-white elevated fundus lesions typically located in the superotemporal quadrant along the superior arcades. The pathology of calcification can be classified as dystrophic, metastatic, or idiopathic. Vision-threatening complications may arise, such as choroidal neovascular membrane and serous retinal detachment. The pathogenesis of sclerochoroidal calcification remains unclear. CASE REPORT: A 72-year-old Caucasian male patient presented to the clinic for routine examination. Fundus evaluation revealed bilateral, multifocal, pale yellow elevated lesions in the superotemporal fundus. Ultrasonography showed a focal area of hyper-reflectivity located in the posterior retina of both eyes, and optical coherence tomography showed an intact retina overlying the elevated lesions in the choroid. Systemic evaluation for dystrophic and metastatic calcification was negative, and the patient was diagnosed with idiopathic sclerochoroidal calcification. CONCLUSIONS: It is important to distinguish sclerochoroidal calcification from other conditions to prevent unnecessary intervention. Calcification of body tissues warrants a systemic evaluation, including screening for calcium and phosphorous levels, to rule out underlying systemic disease. If a biochemical abnormality is discovered, it can be appropriately treated with supplements. If calcification is deemed idiopathic, then annual dilated examinations are recommended to monitor the fundus lesions. Visual prognosis for sclerochoroidal classification is good, as the lesions are typically located away from the macula and foveal encroachment is rare.

Photodynamic therapy for polypoidal choroidal vasculopathy.

The first effective therapy for exudative macular degeneration (AMD) was Photodynamic Therapy (PDT). Diagnosis of the disease was to a large extent by fluorescein angiography (FA). Distinguishing between the leaky choroidal neovessels (CNV) associated with exudative AMD, and the polypoidal structures associated with Polypoidal Choroidal Vasculopathy (PCV) is not always easy using FA alone. The switch to Indocyanine Green angiography helped to pinpoint PCV, and thus to study the efficacy of photodynamic therapy of this particular form of retinal disease, which is more frequently encountered among pigmented individuals. The results appear to be quite promising, and in the year following treatment only a small fraction of the patients had to be retreated. Alternatively, treating PCV with repeated intravitreal VEGF blocking agents was not as successful as it was in the treatment of wet AMD. However, combining PDT-induced angio-occlusion of the polypoidal lesions with anti-vascular endothelial growth factor therapy was shown to be quite effective, and the combination of PDT with an anti-angiogenic agent as well as a steroid, in a triple therapy, was recently also shown to be a quite promising option. In the present article we review the data on PDT of PCV, including combination therapies and alternative treatments. We also report on similarities and differences between AMD and PCV.

Strategy for the management of complex retinal detachments: the European vitreo-retinal society retinal detachment study report 2.

OBJECTIVE: To study the outcome of the treatment of complex rhegmatogenous retinal detachments (RRDs). DESIGN: Nonrandomized, multicenter, retrospective study. PARTICIPANTS: One hundred seventy-six surgeons from 48 countries spanning 5 continents reported primary procedures for 7678 RRDs. METHODS: Reported data included clinical manifestations, the method of repair, and the outcome. MAIN OUTCOME MEASURES: Failure of retinal detachment repair (level 1 failure rate), remaining silicone oil at the study's conclusion (level 2 failure rate), and need for additional procedures to repair the detachments (level 3 failure rate). RESULTS: The main categories of complex retinal detachments evaluated in this investigation were: (1) grade B proliferative vitreoretinopathy (PVR; n = 917), (2) grade C-1 PVR (n = 637), (3) choroidal detachment or significant hypotony (n = 578), (4) large or giant retinal tears (n = 1167), and (5) macular holes (n = 153). In grade B PVR, the level 1 failure rate was higher when treated with a scleral buckle alone versus vitrectomy (P = 0.0017). In grade C-1 PVR, there was no statistically significant difference in the level 1 failure rate between those treated with vitrectomy, with or without scleral buckle, and those treated with scleral buckle alone (P = 0.7). Vitrectomy with a supplemental buckle had an increased failure rate compared with those who did not receive a buckle (P = 0.007). There was no statistically significant difference in level 1 failure rate between tamponade with gas versus silicone oil in patients with grade B or C-1 PVR. Cases with choroidal detachment or hypotony treated with vitrectomy had a significantly lower failure rate versus treatment with scleral buckle alone (P = 0.0015). Large or giant retinal tears treated with vitrectomy also had a significantly lower failure rate versus treatment with scleral buckle (P = 7×10(-8)). CONCLUSIONS: In patients with retinal detachment, when choroidal detachment, hypotony, a large tear, or a giant tear is present, vitrectomy is the procedure of choice. In retinal detachments with PVR, tamponade with either gas or silicone oil can be considered. If a vitrectomy is to be performed, these data suggest that a supplemental buckle may not be helpful. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Coroidopatía serosa central crónica. Tratamiento combinado con Ranibizumab y terapia fotodinámica / Chronic central serous chorioretinopathy. Combined treatment with Ranibizumab and photodynamic therapy

Caso Clínico. Varón de 72 años que acude a consulta refiriendo visión borrosa en ojo derecho (OD) de más de dos años de evolución y que presentaba un desprendimiento neurosensorial (DNS) macular en la tomografía de coherencia óptica (OCT). Habiendo sido diagnosticado previamente de coroidopatía serosa central (CSC) crónica en otro centro y habiendo sido tratado con ranibizumab intravítreo y fotocoagulación láser. Decidimos combinar el tratamiento con ranibizumab intravítreo y terapia fotodinámica para evitar nuevas reactivaciones. Discusión. Tras dos sesiones de terapia fotodinámica junto con tres dosis de Ranibizumab el cuadro se controló estabilizándose la agudeza visual del paciente. Ambas estrategias combinadas dieron buen resultado, disminuyendo el número de brotes en los últimos meses; no obstante debemos continuar con el seguimiento para observar posibles efectos adversos a medio o largo plazo (AU)

Case Report. 72 years-old male who came to our service because of blurred vision in his right eye (OD), and who presented a neurosensorial detachment (NSD) in optical coherence tomography (OCT). Having already been diagnosed in other center of chronic central serous chorioretinopathy and having already been treated with intravitreous Ranibizumab and photocoagulation laser. We decided to combine intravitreous Ranibizumab treatment and photodynamic therapy in order to avoid new reactivations. Discussion. After two photodynamic therapy sessions and three intravitreous Ranibizumab inyections the patient´s visual acuity got stable. We got good results combining both therapeutical strategies, and the number of outbreaks has decreased during the last months; however we should carry on checking our patient to detect any possible half or long term side effects (AU)

Management of inflammatory choroidal neovascularization (CNV) secondary to punctate inner choroidopathy in a young female of childbearing age with intra-vitreal ranibizumab and half-fluence photodynamic therapy (PDT) - a holistic approach.

Choroidal neovascularization (CNV) may occur in up to 40% of patients with punctate inner choroidopathy (PIC). We report a case of a young woman of childbearing age treated successfully for an inflammatory choroidal neovascular membrane (CNV) secondary to PIC with a combination of intravitreal ranibizumab and photodynamic therapy (PDT).

[Surgical management of sub-retinal haemorrhage secondary to polypoidal choroidal vasculopathy]. / Prise en charge chirurgicale des hémorragies sous-rétiniennes secondaires à une vasculopathie polypoïdale.

We report the case of a 34-year-old black woman with acute and severe unilateral loss of sight related to idiopathic polypoidal choroidal vasculopathy responsible for a sub macular haemorrhage (1/10 on the Monoyer scale). The patient underwent a pars plana vitrectomy associated with a sub retinal administration of tissue plasminogen activator (100 µg) and a pneumatic displacement by gas (C2F6) with facedown positioning for 5 days. There were no intraoperative complications and the clot was lysed and totally displaced from the macula. There was no recurrence of the disease and the retinal epithelium detachment decreased progressively. The final visual acuity was 7/10. This case report illustrates the capacity and efficacy of this surgical procedure in the management of sub macular haemorrhage related to polypoidal choroidal vasculopathy. It provides effective displacement of the clot, limiting retinal damage induced by sub macular haemorrhage. Furthermore, it allows early treatment of the polypoidal aneurysm by laser or dynamic phototherapy and increases final visual acuity. Randomised studies are expected to determine the indication for this surgical procedure in the management of polypoidal choroidal vasculopathy and the possible association of laser, dynamic phototherapy, or anti-VEGF treatments.

Occipital porencephaly in a child with gyrate atrophy of the choroid and retina.

A 4-year-old girl was hospitalized for psychomotor delay, low vision, and horizontal nystagmus. She was found to have bilateral chorioretinal atrophic scars and 2 large occipital porencephalic cavities. High plasma ornithine levels led to the presumed diagnosis of gyrate atrophy of the choroid and retina. After 6 months of arginine-restricted diet and high-dose pyridoxine (300 mg/d), there was no change of plasma ornithine level or ocular findings. To our knowledge, this is the first report showing an association of porencephaly with gyrate atrophy of the choroid and retina.

Comparison of photodynamic therapy to transpupillary thermotherapy for polypoidal choroidal vasculopathy.

PURPOSE: To compare the therapeutic efficacy of photodynamic therapy (PDT) to that of transpupillary thermotherapy (TTT) for polypoidal choroidal vasculopathy (PCV). METHODS: PDT or TTT was performed on 46 eyes of 46 patients with PCV; 19 eyes were treated with TTT (TTT group) and 27 eyes with PDT (PDT group). PCV was diagnosed by fundus examination, fluorescein angiography (FA) , and indocyanine green angiography (ICGA) . The best-corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution (logMAR) units and OCT-determined foveal thickness were evaluated before and after treatment. For statistical analyses, the Student's t-test and chi(2) test were used. RESULTS: The number of treatments during the 12-month follow-up period was significantly higher in the TTT group (1.7 times) than in the PDT group (1.3 times; P=0.0134). The difference in the BCVA between the TTT and PDT groups at the baseline was not significant (P=0.3150), but the BCVA in the PDT group was significantly better than that in the TTT group at 3, 6, and 12 months after treatment (P=0.0093, P=0.0074, P=0.0006, respectively). The foveal thickness decreased markedly at 6 months after treatment in the PDT group (P<0.0001) but not significantly in the TTT group (P=0.8982). A vitreous haemorrhage was observed after treatment in two eyes in the TTT group. CONCLUSIONS: BCVA was significantly better and the fovea was significantly thinner in the PDT group than in the TTT group after treatment. Thus, PDT may be more effective than TTT for the treatment of eyes with PCV.

Relation of optical coherence tomography and unusual angiographic leakage patterns in central serous chorioretinopathy.

PURPOSE: To investigate the anatomic basis of atypical angiographic leaks in central serous chorioretinopathy (CSC) with optical coherence tomography (OCT). METHODS: Fluorescein angiography (FA) and OCT were performed in three eyes of three patients (two men, one woman) with CSC. The angiographic leaks were treated with transpupillary thermotherapy (TTT) in two patients with long-standing CSC. The investigations were repeated in the treated patients during follow-up visits. RESULTS: Clinically, all patients demonstrated typical CSC; the female patient had subretinal fibrin under the detachment. FA showed unusual leakage patterns and OCT revealed bridging tissue connecting the pigment epithelial detachment (PED) to the overlying detached retina in all patients. CSC resolved completely in the two patients who underwent TTT along with normalization of the OCT findings. In one patient re-evaluated before complete resolution of CSC, OCT showed a flattened PED with disappearance of the bridging tissue and persistent serous detachment. FA demonstrated conversion of the previously atypical leak into a classic 'smokestack' configuration. Over the next month, leakage resolved completely. CSC and the anatomical findings persisted in the untreated patient. CONCLUSION: OCT identified a potential anatomic basis for unusual angiographic leakage pattern in all three cases of CSC evaluated.