Protocolo de tratamiento del edema macular quístico asociado a retinosis pigmentaria y otras distrofias hereditarias de la retina / Protocol for the treatment of cystoid macular edema secondary to retinitis pigmentosa and other inherited retinal dystrophies

Las distrofias hereditarias de la retina (DHR) son la causa principal de ceguera legal en la población laboral. El edema macular quístico (EMQ) es una de las causas tratables de pérdida visual afectando hasta un 50% de los pacientes. Se ha realizado una revisión bibliográfica combinando «inherited retinal dystrophy», «retinitis pigmentosa», «macular oedema» y un protocolo diagnóstico/terapéutico según los niveles de evidencia y recomendaciones de la «US Agency for Healthcare Research and Quality». Este protocolo se ha discutido en las reuniones mensuales del grupo XAREA DHR con la participación de más de 25 profesionales, creando un documento de consenso. La etiología del EMQ es multifactorial: disfunción de la barrera hematorretiniana, del epitelio pigmentario de la retina y de las células de Müller, inflamación y tracción vítrea. La OCT es la prueba de elección para el diagnóstico y seguimiento del EMQ asociado a las DHR. Los fármacos con mayor grado de evidencia científica son los inhibidores de la anhidrasa carbónica (IAC). Los corticoides, anti-VEGF intravítreos y vitrectomía con pelado de la membrana limitante interna no disponen de suficiente evidencia. Se propone un esquema de tratamiento en el EMQ en las DHR en adultos, otro para pacientes pediátricos y otra en las DHR y cirugía de catarata. Los IAC orales y tópicos son efectivos en el tratamiento del EMQ secundario a las DHR. El tratamiento con corticoides, anti-VEGF y vitrectomía son opciones de segunda línea. Se requieren ensayos clínicos aleatorizados para poder establecer la escala terapéutica en estos pacientes.(AU)

Inherited retinal dystrophies (IRD) are the leading cause of legal blindness in the working population. Cystic macular edema (CME) is one of the treatable causes of visual loss, affecting up to 50% of the patients. A bibliographic review has been carried out combining “inherited retinal dystrophy”, “retinitis pigmentosa”, “macular edema” and a diagnostic-therapeutic protocol according to the levels of evidence and recommendations of the “US Agency for Healthcare Research and Quality”. This protocol has been discussed in the monthly meetings of the XAREA DHR group with the participation of more than 25 experts, creating a consensus document. The etiology of CME is multifactorial: dysfunction of the blood-retinal barrier, retinal pigment epithelium, and Müller cells, inflammation, and vitreous traction.OCT is the test of choice for the diagnosis and follow-up of CME associated with IRD. The drugs with the highest degree of scientific evidence are carbonic anhydrase inhibitors (IAC). Intravitreal corticosteroids, anti-VEGF, and vitrectomy with peeling of the internal limiting membrane do not have sufficient evidence. A treatment scheme is proposed for the CME in IRD in adults, another for pediatric patients and an another for IRD and cataract surgery. Oral and topical IACs are effective in the treatment of CME secondary to IRD. Treatment with corticosteroids, anti-VEGF, and vitrectomy are second-line options. Randomized clinical trials are required to establish the therapeutic scale in these patients.(AU)

Protocol for the treatment of cystoid macular edema secondary to retinitis pigmentosa and other inherited retinal dystrophies.

Inherited retinal dystrophies (IRD) are the leading cause of legal blindness in the working population. Cystic macular edema (CME) is one of the treatable causes of visual loss, affecting up to 50% of the patients. A bibliographic review has been carried out combining "inherited retinal dystrophy", "retinitis pigmentosa", "macular oedema" and a diagnostic-therapeutic protocol according to the levels of evidence and recommendations of the "US Agency for Healthcare Research and Quality". This protocol has been discussed in the monthly meetings of the XAREA DHR group with the participation of more than 25 ophthalmologists, creating a consensus document. The etiology of CME is multifactorial: dysfunction of the blood-retinal barrier, retinal pigment epithelium, and Müller cells, inflammation, and vitreous traction. OCT is the test of choice for the diagnosis and follow-up of CME associated with IRD. The drugs with the highest degree of scientific evidence are carbonic anhydrase inhibitors (IAC). Intravitreal corticosteroids, anti-VEGF, and vitrectomy with peeling of the internal limiting membrane do not have sufficient evidence. A treatment scheme is proposed for the CME in IRD in adults, another for pediatric patients and another for IRD and cataract surgery. Oral and topical IACs are effective in the treatment of CME secondary to IRD. Treatment with corticosteroids, anti-VEGF, and vitrectomy are second-line options. Randomized clinical trials are required to establish the therapeutic scale in these patients.

Optimizing the storage of chemotherapeutics for ophthalmic oncology: stability of topotecan solution for intravitreal injection.

BACKGROUND: . Intravitreal administration of topotecan shows activity against tumor vitreous seeding in the conservative treatment of retinoblastoma, a malignant tumor originated in the retina of small children. Adequate storage of the intravitreal topotecan solution would allow immediate availability for patients at health care institutions. The goal of the work was to address the stability of the intravitreal topotecan formulation upon reconstitution. MATERIALS AND METHODS: . Intravitreal topotecan solutions were reconstituted (at a concentration of 0.2 mg topotecan in 1 mL saline solution vehicle, aliquoted in 1 mL plastic syringes) and stored either frozen or at room temperature for different times. Topotecan content was analyzed at time zero and at different conditions using a high performance liquid chromatography method to quantify topotecan lactone (active) and to detect its pH-dependent hydrolysis product, the open carboxylate. RESULTS: . We found that intravitreal topotecan syringes remained stable at room temperature at least for 24 h, at least for 167 days upon stored frozen at -20°C, and up to 8 h after thawing at day 6. The degradation carboxylate product did not appear in the analyzed thawed samples during the whole study. CONCLUSIONS: . This study confirms the stability of frozen intravitreal topotecan syringes and will help optimize the use of this chemotherapy modality at institutions with low resources. Storage of aliquots will also help reduce personnel exposure to chemotherapy at hospital pharmacies.

Swept-source and optical coherence tomography angiography in patients with X-linked retinoschisis.

PurposeTo explore the structural features of juvenile X-linked retinoschisis (XLRS) using swept-source-optical coherence tomography (SS-OCT) and optical coherence tomography angiography (OCT-A).DesignRetrospective, observational cross-sectional study.Patients and methodsNine patients (18 eyes) diagnosed with juvenile XLRS were included. SS-OCT and OCT-A were used to evaluate the characteristics of the inner/outer retina and the choroid.ResultsSS-OCT showed that the inner nuclear layer (INL) was the most commonly affected area (16/18 eyes; 89%). No significant differences in central macular thickness (CMT) or subfield choroidal thickness (SFCT) were evidenced between eyes (CMT: 364 µm in the right eye vs 320 µm in the left eye; SFCT: 305 vs 307 µm; P=0.895). Best-corrected visual acuity (BCVA) did not correlate with CMT (rs= -0.19; P=0.445) or SFCT (rs=0.06; P=0.795). BCVA was significantly correlated with the following defects: outer plexiform layer (OPL; rs=0.50; P=0.036); external limiting membrane (ELM; rs=0.65; P=0.003); ellipsoid portion of inner segment (EPIS; rs=0.67; P=0.002); and the cone outer segment tips (COST; rs=0.69; P=0.001). Schisis at the INL revealed a spoke-like pattern in the foveal region and a reticular pattern in the parafoveal region on en-face imaging. In cases in which the schisis affected the OPL, multiple polygonal hyporeflective cavities were observed in the foveal region.ConclusionsThe hyporeflective spaces on SS-OCT were primarily located at the INL and OPL. BCVA did not correlate with CMT or SFCT; however, ELM, EPIS, and COST defects were significantly correlated with worse BCVA. There was a positive correlation between age and SFCT.

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)

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

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.

Déficit de 3-hidroxiacil-CoA-deshidrogenasa de cadena larga: a propósito de un caso / Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: A case report

CASO CLÍNICO: Paciente de 5 años de edad remitido para valoración oftalmológica con el diagnóstico de déficit de 3-hidroxiacil-CoA deshidrogenasa de cadena larga. Presentaba como antecedente la aparición de crisis metabólicas agudas precipitadas por infecciones banales y rabdomiólisis. El examen oftalmoscópico reveló una atrofia coriorretiniana peripapilar y una maculopatía granular difusa. La agudeza visual era de 6/6 en ambos ojos y las pruebas electrofisiológicas normales. DISCUSIÓN: Se realiza una revisión de la bibliografía y los conocimientos recientes de esta enfermedad mediante la descripción de un caso clínico documentando los hallazgos obtenidos mediante autofluorescencia y tomografía de coherencia óptica para mejorar el conocimiento existente sobre ella

CLINICAL CASE: A five-year-old patient, with a diagnosis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, was referred for an ophthalmological examination. He had a history of acute metabolic crises precipitated by intercurrent infections,as well as rhabdomyolysis. The fundoscopic examination revealed a peripapillary chorioretinal atrophy and a diffuse granular appearance of the macular retinal pigment epithelium. Best corrected visual acuity was 6/6 in both eyes, and he had a normal electroretinography test. DISCUSSION: We perform a review of the literature and recent findings in relation to this disease through the description of a clinical case in order to improve the knowledge of this uncommon disorder

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: A case report. / Déficit de 3-hidroxiacil-CoA-deshidrogenasa de cadena larga: a propósito de un caso.

CLINICAL CASE: A five-year-old patient, with a diagnosis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, was referred for an ophthalmological examination. He had a history of acute metabolic crises precipitated by intercurrent infections,as well as rhabdomyolysis. The fundoscopic examination revealed a peripapillary chorioretinal atrophy and a diffuse granular appearance of the macular retinal pigment epithelium. Best corrected visual acuity was 6/6 in both eyes, and he had a normal electroretinography test. DISCUSSION: We perform a review of the literature and recent findings in relation to this disease through the description of a clinical case in order to improve the knowledge of this uncommon disorder.

Preoperative study of the inner segment/outer segment junction of photoreceptors by spectral-domain optical coherence tomography as a prognostic factor in patients with epiretinal membranes.

OBJECTIVE: To demonstrate whether the preoperative integrity of the inner segment/outer segment (IS/OS) junction of photoreceptors studied by spectral-domain optical coherence tomography (SD-OCT) is a prognostic factor in epiretinal membrane surgery. METHODS: We retrospectively studied patients with an idiopathic epiretinal membrane who underwent a 23-gauge vitrectomy to remove this membrane. Best-corrected visual acuity (BCVA) and SD-OCT scans were examined before and 6 months after the surgery. We studied the retinal microstructure, especially the IS/OS junction of the photoreceptors, and evaluated the intergroup differences between patients with an intact layer and those with an irregular or disrupted layer. We applied both the Wilcoxon and Mann-Whitney tests for statistical analysis. RESULTS: In total, 51 eyes from 51 enrolled patients were examined in this study. The postoperative BCVA was significantly better for eyes that had an intact IS/OS junction than for eyes that had an irregular or disrupted IS/OS junction, as preoperatively observed with SD-OCT scans (P < 0.001). We also observed an important association between disrupted IS/OS junctions and the presence of cystic macular edema (P < 0.01). CONCLUSION: The presence of an intact IS/OS junction on the preoperative SD-OCT scan was an important predictor of better visual recovery after epiretinal membrane surgery.

[Uveitis masquerade syndrome as a presenting form of diffuse retinoblastoma]. / Síndrome Mascarada por retinoblastoma difuso.

CLINIC REPORT: A 3-year-old boy presented with an intermediate uveitis. Complete ophthalmic exam, ocular ultrasonography, magnetic resonance imaging and computerized tomography of the orbit were inconclusive. Determination of the aqueous humor/serum rate of Lactate dehydrogenase (LDH) was the key for the diagnosis of a diffuse retinoblastoma. DISCUSSION: A masquerade syndrome is the initial presentation in 1-3% of retinoblastomas. Aqueous humor punction is contraindicated in patients with retinoblastoma but it might be the only way to achieve a correct diagnosis in these difficult and very unusual cases: enzymatic assays such as LDH offer a good sensitivity and specificity for the diagnosis of these patients.

Síndrome mascarada por retinoblastoma difuso / Uveitis masquerade syndrome presenting as a diffuse retinoblastoma

Caso clínico: Paciente de tres años con sospecha deuveítis intermedia. La exploración oftalmológica,ecografía ocular, resonancia nuclear magnética ytomografía computerizada orbitaria no fueron concluyentes.La determinación de la tasa de lactatodeshidrogenasa (LDH) en humor acuoso/suero fuela clave para llegar al diagnóstico de un retinoblastomadifuso.Discusión: El síndrome mascarada es la forma dedebut en un 1-3% de los retinoblastomas. La punciónde cámara anterior está contraindicada enpacientes con retinoblastoma pero podría ser la únicaforma de llegar a un diagnóstico correcto enestos casos difíciles y poco frecuentes. Las pruebasenzimáticas como la LDH nos ofrecen una buenasensibilidad y especificidad para el diagnóstico de estos pacientes(AU)

Clinic report: A 3-year-old boy presented with anintermediate uveitis. Complete ophthalmic exam,ocular ultrasonography, magnetic resonance imagingand computerized tomography of the orbitwere inconclusive. Determination of the aqueoushumor/serum rate of Lactate dehydrogenase (LDH)was the key for the diagnosis of a diffuse retinoblastoma.Discussion: A masquerade syndrome is the initialpresentation in 1-3% of retinoblastomas. Aqueoushumor punction is contraindicated in patients withretinoblastoma but it might be the only way toachieve a correct diagnosis in these difficult andvery unusual cases: enzymatic assays such as LDHoffer a good sensitivity and specificity for the diagnosisof these patients(AU)

[Multifocal electroretinogram and age-related macular degeneration]. / Electrorretinograma multifocal y degeneración macular asociada a la edad.

PURPOSE: To assess the value of multifocal electroretinogram (mfERG) in clinical evaluation of the response of patients with choroidal neovascularization (CNV), secondary to age-related macular degeneration, to photodynamic therapy (PDT). METHODS: We designed a prospective non-comparative case series and enrolled 23 eyes of 22 patients with predominantly classic CNV. The initial evaluation included clinical examination with measurement of visual acuity (Colenbrander), biomicroscopic evaluation (BMC), retinography, fluorescein angiography (FA), Humphrey 24-2 visual field examination and mfERG. All patients were treated with PDT. Clinical follow-up was performed two and six months after treatment with visual acuity evaluation, BMC, visual field assessment and mfERG. FA was repeated after an interval of between four and six months in all patients. RESULTS: Visual acuity remained stable or improved in all patients included in the study. Visual field examination gave erratic and unreliable results because of patients' unstable fixation. N1 and P1 wave peak amplitudes in the central rings did not change significantly after treatment but they improved in rings 3 (p=0.000), 4 and 5 (p=0.008). CONCLUSIONS: Multifocal ERG is a useful tool for the clinical follow-up of CNV. It offers interesting non-subjective data of retinal sensitivity of patients with macular diseases treated with PDT. In addition we obtained a central retinal sensitivity map where we were able to evaluate the extent and depth of retinal damage.

Electrorretinograma multifocal y degeneración macular asociada a la edad / Multifocal electroretinogram and age-related macular degeneration

Objetivo: Determinar la utilidad del electrorretinograma multifocal (mfERG) en la evaluación clínica de la respuesta al tratamiento con terapia fotodinámica (TFD) en pacientes con neovascularización coroidea (NVC) secundaria a degeneración macular asociada a la edad (DMAE).Métodos: Se ha realizado un estudio prospectivo en 23 ojos de 22 pacientes con NVC predominantemente clásica. Al inicio se realizó una medición de la agudeza visual mediante optotipos de Colenbrander, exploración biomicroscópica (BMC), retinografía, angiografía fluoresceínica (AGF), campimetría de Humphrey 24-2 y mfERG. Todos los pacientes fueron tratados mediante TFD. Se ha repetido la exploración de la agudeza visual, BMC, campimetría y mfERG a los dos y a los seis meses del tratamiento y se ha realizado una AGF tras un intervalo entre los cuatro y seis meses del inicio del estudio.Resultados: La agudeza visual permanece estable o mejora en todos los pacientes incluidos en el estudio. El estudio campimétrico nos ofrece resultados erráticos y poco fiables debido a la mala fijación que presentan estos pacientes. La densidad de respuesta de las ondas N1 y P1 del mfERG en los anillos centrales no muestra variaciones significativas después del tratamiento, sin embargo mejora en los anillos 3 (p=0,000), 4 y 5 (p=0,008).Conclusiones: El mfERG es una prueba de utilidad en el seguimiento de la NVC puesto que nos permite medir objetivamente la sensibilidad retiniana en pacientes con maculopatías tratadas con terapia fotodinámica. Por otra parte obtenemos un mapa de sensibilidades de la retina central en el que podemos valorar la extensión y la profundidad de la lesión

Purpose: To assess the value of multifocal electroretinogram (mfERG) in clinical evaluation of the response of patients with choroidal neovascularization (CNV), secondary to age-related macular degeneration, to photodynamic therapy (PDT) Methods: We designed a prospective non-comparative case series and enrolled 23 eyes of 22 patients with predominantly classic CNV. The initial evaluation included clinical examination with measurement of visual acuity (Colenbrander), biomicroscopic evaluation (BMC), retinography, fluorescein angiography (FA), Humphrey 24-2 visual field examination and mfERG. All patients were treated with PDT. Clinical follow-up was performed two and six months after treatment with visual acuity evaluation, BMC, visual field assessment and mfERG. FA was repeated after an interval of between four and six months in all patients. Results: Visual acuity remained stable or improved in all patients included in the study. Visual field examination gave erratic and unreliable results because of patients’ unstable fixation. N1 and P1 wave peak amplitudes in the central rings did not change significantly after treatment but they improved in rings 3 (p=0.000), 4 and 5 (p=0.008). Conclusions: Multifocal ERG is a useful tool for the clinical follow-up of CNV. It offers interesting non-subjective data of retinal sensitivity of patients with macular diseases treated with PDT. In addition we obtained a central retinal sensitivity map where we were able to evaluate the extent and depth of retinal damage