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Purpose: To describe the clinical and genetic characteristics (mutation in RS1 gene) of a Spanish family with X-linked retinoschisis (XLRS) associated with retinitis punctata albescens (RPA). Methods: The detailed ophthalmological examination included best corrected visual acuity (BCVA), colour and autofluorescence photography, fluorescein angiography, optical coherence tomography and electrophysiology tests. A next-generation sequencing (NGS) strategy was applied to the index patient, and then sequenced in an Illumina NextSeq500 system. Candidate variants considered to be disease-causing in the patient were confirmed and segregated in the family by Sanger sequencing. Results: We have studied three siblings of 54, 59 and 50 years old. Two of them presented with macular foveoschisis and a whitish mottling of the pigment epithelium in the peripheral and equatorial retina, while the other had macular atrophy. Electroretinography revealed a reduced b-wave, while a-wave remained unchanged. Mutation in RS1 (c.98G>A; p.Trp33*) was identified as the cause of the disease. Conclusion: XLRS is a genetic disease that leads to irreversible visual loss. We describe an unusual phenotype manifestation of a known mutation.

[EN] Mutations in the ABCA4 gene are a common cause of Stargardt disease; however, other retinal phenotypes have also been associated with mutations in this gene. We describe an observational case report of an unusual clinical phenotype of Stargardt disease. The ophthalmological examination included best corrected visual acuity, color and autofluorescence photography, fluorescein angiography, optical coherence tomography, and electrophysiology tests. Targeted next-generation sequencing of 99 genes associated with inherited retinal dystrophies was performed in the index patient. A 48-year-old woman presented with a best corrected visual acuity of 20/25 and 20/20. Fundoscopy revealed perifoveal yellow flecked-like lesions. Fluorescein angiography and fundus autofluorescence findings were consistent with pattern dystrophy. Pattern electroretinogram demonstrated bilateral decrease of p50 values. Genetic testing identified two heterozygous missense mutations, c.428C>T, p.(Pro143Leu) and c.3113C>T, p.(Ala.1038Val), in the ABCA4 gene. Based on our results, we believe that these particular mutations in the ABCA4 gene could be associated with a specific disease phenotype characterized by funduscopic appearance similar to pattern dystrophy. A detailed characterization of the retinal phenotype in patients carrying specific mutations in ABCA4 is crucial to understand disease expression and ensure optimal clinical care for patients with inherited retinal dystrophies. [PT] Mutações no gene ABCA4 são causa comum da doença de Stargardt, mas outros fenótipos da retina também foram associados a mutações nesse gene. Apresentamos um relato de caso observacional de um fenótipo clínico incomum da doença de Stargardt. O exame oftalmológico incluiu a acuidade visual com melhor correção, fotografia em cores e com autofluorescência, angiofluoresceinografia, tomografia de coerência óptica e testes de eletrofisiologia. Na paciente em questão, realizou-se o sequenciamento de próxima geração de 99 genes associados a distrofias retinais hereditárias. Tratava-se de uma mulher de 48 anos com melhor acuidade visual corrigida de 20/25 e 20/20. A fundoscopia revelou lesões puntiformes amarelas perifoveais. Os resultados da angiofluoresceinografia e da autofluorescência do fundo de olho foram consistentes com distrofia em padrão. A eletrorretinografia por padrões mostrou diminuição bilateral dos valores de p50. Os testes genéticos revelaram duas mutações missense heterozigóticas, c.428C>T, p. (Pro143Leu) e c.3113C>T, p. (Ala.1038Val), no gene ABCA4. Nossos resultados nos fazem pensar que essas mutações específicas em ABCA4 talvez possam estar associadas a um fenótipo específico da doença, caracterizado por uma aparência fundoscópica semelhante à da distrofia em padrão. Uma caracterização detalhada do fenótipo da retina em pacientes portadores de mutações específicas em ABCA4 é crucial para compreender a expressão da doença e para garantir o tratamento clínico ideal para pacientes com distrofias retinais hereditárias. This work was supported by Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness and co-funded by European Union (ERDF, “A way to make Europe”) [PI15-01648] and [PI1800612]; regional Ministry of Economy, Innovation, Science and Employment [CTS-1664] and regional Ministry of Health and Families [PEER-0501-2019] of the Autonomous Government of Andalusia; Foundation Isabel Gemio/Foundation Cajasol [FGEMIO-2019-01].

[Purpose] To describe the clinical and genetic characteristics (novel mutation in BEST1 gene) of a Spanish patient with autosomal recessive bestrophinopathy (ARB)., [Methods] The detailed ophthalmological examination included best corrected visual acuity (BCVA), color and autofluorescence photography, fluorescein angiography, optical coherence tomography, and electrophysiology tests. A next-generation sequencing (NGS) strategy was applied to the index patient, and then sequenced in an Illumina NextSeq500 system., [Results] A 55-year-old male presented with a BCVA of 20/25 in the right eye and 20/20 in the left eye. Fundoscopy revealed perifoveal yellow flecked-like lesions. Fluorescein angiography and fundus autofluorescence results were consistent with pattern dystrophy. A homozygous frameshift mutation in BEST1 (c.341_342del; p.(Leu114Glnfs*57)) was identified as the cause of the disease., [Conclusion] ARB is a genetic disease that leads to irreversible visual loss. In this report we found a novel mutation responsible for this disease.

Seven patients (14 eyes) diagnosed with X-linked ichthyosis were studied using the Schirmer test, biomicroscopy, tonometry, endothelial count, optical coherence tomography, Pentacam®, ocular surface analyser, and confocal microscopy. The mean age was 33.83±20.17 years (range: 7-64 years). The most frequent findings in biomicroscopy were Meibomian glands dysfunction (83.3%) and stromal corneal opacities (33%). The tear break-up time was found shortened in 25% of the eyes. Confocal microscopy (both eyes) revealed activated keratocytes with hyper-reflective particles inside them in the anterior stroma and outside them in the posterior stroma. It is believed that the inclusion of the use of confocal microscopy will help in a better understanding of the corneal pathology associated with ichthyosis X, as well as new characteristics of these patients.

Resumen Se estudio a 7 pacientes (14 ojos) diagnosticados de ictiosis X mediante test de Schirmer, biomicroscopia, tonometria, recuento endotelial, tomografia de coherencia optica, Pentacam, analizador de superficie ocular y microscopia confocal. La edad media fue 33,83 ± 20,17 anos (rango: 7-64 anos). Los hallazgos mas frecuentes en biomicrocoscopia fueron disfuncion de glandulas de Meibomio (83,3%) y opacidades corneales estromales (33%). El tiempo de rotura de la pelicula lagrimal se encontro acortado en el 25% de los ojos. La microscopia confocal (2 ojos) revelo queratocitos activados con particulas hiperreflectivas en su interior en estroma anterior y fuera de ellos en estroma posterior. Creemos que la extension del uso de la microscopia confocal permitira conocer mejor la enfermedad corneal asociada a ictiosis X y nuevas caracteristicas de estos pacientes.

To enhance the use of Whole Genome Sequencing (WGS) in clinical practice, it is still necessary to standardize data analysis pipelines. Herein, we aimed to define a WGS-based algorithm for the accurate interpretation of variants in inherited retinal dystrophies (IRD). This study comprised 429 phenotyped individuals divided into three cohorts. A comparison of 14 pathogenicity predictors, and the re-definition of its cutoffs, were performed using panel-sequencing curated data from 209 genetically diagnosed individuals with IRD (training cohort). The optimal tool combinations, previously validated in 50 additional IRD individuals, were also tested in patients with hereditary cancer (n = 109), and with neurological diseases (n = 47) to evaluate the translational value of this approach (validation cohort). Then, our workflow was applied for the WGS-data analysis of 14 individuals from genetically undiagnosed IRD families (discovery cohort). The statistical analysis showed that the optimal filtering combination included CADDv1.6, MAPP, Grantham, and SIFT tools. Our pipeline allowed the identification of one homozygous variant in the candidate gene CFAP20 (c.337 C > T; p.Arg113Trp), a conserved ciliary gene, which was abundantly expressed in human retina and was located in the photoreceptors layer. Although further studies are needed, we propose CFAP20 as a candidate gene for autosomal recessive retinitis pigmentosa. Moreover, we offer a translational strategy for accurate WGS-data prioritization, which is essential for the advancement of personalized medicine., This work was supported by the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness, Spain and co-funded by the European Union (ERDF, “A way to make Europe”) [PI18-00612; PI21-00244], Regional Ministry of Health and Families of the Autonomous Government of Andalusia [PEER-0501-2019] and the Foundation Isabel Gemio/Foundation Cajasol [FGEMIO-2019-01]. EFS is supported by fellowship FI19/00091 from ISCIII (ESF, “Investing in your future”). MMS is supported by a fellowship associated with the CTS-1664 project, which has been funded by the Regional Ministry of Economy, Knowledge, Enterprise, and the University of the Regional Government of Andalusia. NBG is supported by a fellowship RH-0118-2020, which has been funded by the Regional Ministry of Health and Families of the Autonomous Government of Andalusia.

Currently, brachytherapy is the most commonly used therapeutic approach for uveal melanomas. Surgical resection by means of endoresection or exoresection is an alternative approach. The present report recounts our experience over 15 years in the treatment of uveal melanoma using a combined approach of resection surgery with brachytherapy. This is a single-center observational retrospective cohort study in which we describe clinical outcomes, complications and survival in 35 cases of melanoma of the iris or the ciliary body after a combination of surgery and brachytherapy or brachytherapy alone. Local treatment of the tumor was successful in all cases with surgery and brachytherapy. The most frequent complications were scleromalacia, bullous keratopathy, retinal toxicity, cataracts, hypotonia, and photophobia. There were three cases of recurrence, all of which were found in the group of patients who had received brachytherapy alone, and in one case we had to perform a secondary enucleation due to tumor growth after brachytherapy. At present, only one patient has died during follow-up due to liver metastases six years after the start of treatment. In carefully selected patients, this approach can be effective and safe, as long as a close follow-up is carried out after surgery.

Purpose In limbal stem cell deficiency, both the Ocular Surface Disease Index (OSDI) questionnaire and tear break-up time (BUT) are comparable between traditional methods and the Keratograph 5M. In this study, we aimed to correlate OSDI with Keratograph 5M interviewed OSDI, as well as slit-lamp tear BUT with Keratograph 5M noninvasive tear break-up time (NIKBUT) in limbal stem cell deficiency. Patients and methods Thirty-eight limbal stem cell-deficiency patients (76 eyes) from Virgen Macarena-Rocio Hospital (Seville, Spain) underwent this diagnostic test study. All patients completed the traditional OSDI. We measured the BUT, performed a Keratograph 5M analysis of NIKBUT first (employed for the analysis) followed by the average NIKBUT, the level of dryness, and conducted the OSDI questionnaire through an interview. For each pair of tests, we analyzed the means and applied an intraclass correlation coefficient (r), creating a Bland-Altman plot for data dispersion. Results Average values were 47.5 points (±25.8), and 47.3 points (±27.5) for traditional OSDI and Keratograph OSDI, respectively (P =0.87); the r value indicates good agreement (0.72). The Bland-Altman plot followed a linear pattern, and the results were similarly distributed. The NIKBUT mean was shorter than the BUT mean (P = 0.007); the r value indicates moderate agreement (0.574). The Bland-Altman plot formed an almost horizontal line, with almost all values between the mean and two standard deviations. Conclusion Keratograph 5M is useful for the evaluation of the ocular surface in limbal stem cell deficiency. NIKBUT can substitute BUT based on its advantages of being noninvasive, objective, with intraobserver and interobserver repeatability and reliability. The Keratograph 5M OSDI is comparable to the traditional questionnaire.

[Aim] To assess the relationship between choroidal thickness and renal function in diabetic patients., [Methods] Cross-sectional retrospective clinical study of 42 eyes of 21 ocular treatment-na?ve diabetic patients. Demographic data included: age, sex, type and course of diabetes. Ocular data included: severity of diabetic retinopathy; retinal thickness at the central macular region, as well as choroidal thickness at the central and paracentral quadrants, using automatically generated maps by swept-source optical coherence tomography; presence of cystic macular edema; and ocular axial length (AXL). Lab-test parameters included: glycated hemoglobin (HbA1c), albuminuria, albumin/creatinine ratio in urine, and glomerular filtration rate., [Results] A significant negative correlation was mainly observed between several choroidal thicknesses, age (P, [Conclusion] Choroidal thickness can represent an additional tool to help clinicians predicting the renal status in ocular treatment-naïve diabetic patients., OFTARED “RD16/0008/0010”, funded by Instituto de Salud Carlos III, integrated in the national I+D+i 2013-2016 and co-funded by European Union (ERDF/ESF, “Investing in your future”).

Background: To characterize the phenotype and genotype of a rare syndrome associating posterior microphthalmos (PM), retinitis pigmentosa (RP), and foveoschisis in a consanguineous Spanish family. Methods: The study involved five family members, consisting of three siblings and their parents. All members underwent comprehensive eye examinations for best corrected visual acuity, axial length and refractive error, electroretinography (ERG), fundus photography, retinal fluorescein angiography (FA), and optical coherence tomography (OCT). Clinical exome sequencing of more than 6,000 clinically relevant genes (SureSelect Focused Exome, Agilent) was performed using the Illumina HiSeq 3000 system. Candidate variants were validated and segregated by Sanger sequencing. Results: The affected siblings had bilateral shortening of the posterior ocular segment and normal anterior segment dimensions. The fundoscopy, ERG, and FA results were compatible with RP. Macular OCT analysis revealed schisis of the outer retinal layer. Our data analysis pipeline identified a homozygous frameshift mutation in exon 5 of the membrane frizzled-related protein (MFRP) gene (c.498delC; p.Asn167Thrfs*25). Conclusion: Our study confirmed the association of PM with RP as an autosomal recessive syndrome. Although this has previously been described, it seems that there are some constant (i.e., PM and RP) and some variable features (i.e., optic nerve drusen and foveoschisis). The MFRP mutation has also been detected in other studies associating PM with RP. Analysis of a larger series of cases at the clinical and genetic levels would certainly help us to better understand the phenotype-genotype correlations of this syndrome.

[EN] Mutations in the ABCA4 gene are a common cause of Stargardt disease; however, other retinal phenotypes have also been associated with mutations in this gene. We describe an observational case report of an unusual clinical phenotype of Stargardt disease. The ophthalmological examination included best corrected visual acuity, color and autofluorescence photography, fluorescein angiography, optical coherence tomography, and electrophysiology tests. Targeted next-generation sequencing of 99 genes associated with inherited retinal dystrophies was performed in the index patient. A 48-year-old woman presented with a best corrected visual acuity of 20/25 and 20/20. Fundoscopy revealed perifoveal yellow flecked-like lesions. Fluorescein angiography and fundus autofluorescence findings were consistent with pattern dystrophy. Pattern electroretinogram demonstrated bilateral decrease of p50 values. Genetic testing identified two heterozygous missense mutations, c.428C>T, p.(Pro143Leu) and c.3113C>T, p.(Ala.1038Val), in the ABCA4 gene. Based on our results, we believe that these particular mutations in the ABCA4 gene could be associated with a specific disease phenotype characterized by funduscopic appearance similar to pattern dystrophy. A detailed characterization of the retinal phenotype in patients carrying specific mutations in ABCA4 is crucial to understand disease expression and ensure optimal clinical care for patients with inherited retinal dystrophies., [PT] Mutações no gene ABCA4 são causa comum da doença de Stargardt, mas outros fenótipos da retina também foram associados a mutações nesse gene. Apresentamos um relato de caso observacional de um fenótipo clínico incomum da doença de Stargardt. O exame oftalmológico incluiu a acuidade visual com melhor correção, fotografia em cores e com autofluorescência, angiofluoresceinografia, tomografia de coerência óptica e testes de eletrofisiologia. Na paciente em questão, realizou-se o sequenciamento de próxima geração de 99 genes associados a distrofias retinais hereditárias. Tratava-se de uma mulher de 48 anos com melhor acuidade visual corrigida de 20/25 e 20/20. A fundoscopia revelou lesões puntiformes amarelas perifoveais. Os resultados da angiofluoresceinografia e da autofluorescência do fundo de olho foram consistentes com distrofia em padrão. A eletrorretinografia por padrões mostrou diminuição bilateral dos valores de p50. Os testes genéticos revelaram duas mutações missense heterozigóticas, c.428C>T, p. (Pro143Leu) e c.3113C>T, p. (Ala.1038Val), no gene ABCA4. Nossos resultados nos fazem pensar que essas mutações específicas em ABCA4 talvez possam estar associadas a um fenótipo específico da doença, caracterizado por uma aparência fundoscópica semelhante à da distrofia em padrão. Uma caracterização detalhada do fenótipo da retina em pacientes portadores de mutações específicas em ABCA4 é crucial para compreender a expressão da doença e para garantir o tratamento clínico ideal para pacientes com distrofias retinais hereditárias., This work was supported by Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness and co-funded by European Union (ERDF, “A way to make Europe”) [PI15-01648] and [PI1800612]; regional Ministry of Economy, Innovation, Science and Employment [CTS-1664] and regional Ministry of Health and Families [PEER-0501-2019] of the Autonomous Government of Andalusia; Foundation Isabel Gemio/Foundation Cajasol [FGEMIO-2019-01].

To describe the clinical and genetic characteristics (novel mutation inThe detailed ophthalmological examination included best corrected visual acuity (BCVA), color and autofluorescence photography, fluorescein angiography, optical coherence tomography, and electrophysiology tests. A next-generation sequencing (NGS) strategy was applied to the index patient, and then sequenced in an Illumina NextSeq500 system.A 55-year-old male presented with a BCVA of 20/25 in the right eye and 20/20 in the left eye. Fundoscopy revealed perifoveal yellow flecked-like lesions. Fluorescein angiography and fundus autofluorescence results were consistent with pattern dystrophy. A homozygous frameshift mutation inARB is a genetic disease that leads to irreversible visual loss. In this report we found a novel mutation responsible for this disease.

La COVID-19 (enfermedad por coronavirus 2019) nos plantea nuevos retos en nuestra rutina diaria. La última cifra publicada de sanitarios contagiados –se dejó de publicar por última vez el 18 de mayo– fue de 51,090 en total y 152 casos nuevos ese mismo día1. Por ello, debemos aprender a protegernos para continuar con nuestra rutina diaria quirúrgica lo más cercana a la normalidad preexistente.

Background: We report a Spanish family, comprising an affected mother and daughter, respectively diagnosed with retinitis pigmentosa and Stargardt-like macular dystrophy, in whom we identified a PROM1 mutation. Methods: A custom gene panel consisting of 119 inherited retinal dystrophies (IRD)-genes was applied in the two affected individuals of this family and sequenced using the Illumina´s NextSeq500 platform. Results: The analysis of the resulting data allowed us to identify the pathogenic PROM1 mutation c.1117C>T (p.Arg373Cys) as the primary cause of the disease in both patients. No additional variants contributing to the extent of retinal dysfunction were detected. Conclusion: The variable expressivity of the detected PROM1 mutation is the most likely responsible for the intrafamilial phenotypic variability observed in this family. Screening of this mutation should be considered in patients with compatible clinical manifestations, especially when accompanied by an autosomal dominant family history.

This article belongs to the Special Issue Inherited Retinal Diseases., The management of unsolved inherited retinal dystrophies (IRD) cases is challenging since no standard pipelines have been established. This study aimed to define a diagnostic algorithm useful for the diagnostic routine and to address unsolved cases. Here, we applied a Next-Generation Sequencing-based workflow, including a first step of panel sequencing (PS) followed by clinical-exome sequencing (CES) and whole-exome sequencing (WES), in 46 IRD patients belonging to 42 families. Twenty-six likely causal variants in retinal genes were found by PS and CES. CES and WES allowed proposing two novel candidate loci (WDFY3 and a X-linked region including CITED1), both abundantly expressed in human retina according to RT-PCR and immunohistochemistry. After comparison studies, PS showed the best quality and cost values, CES and WES involved similar analytical efforts and WES presented the highest diagnostic yield. These results reinforce the relevance of panels as a first step in the diagnostic routine and suggest WES as the next strategy for unsolved cases, reserving CES for the simultaneous study of multiple conditions. Standardizing this algorithm would enhance the efficiency and equity of clinical genetics practice. Furthermore, the identified candidate genes could contribute to increase the diagnostic yield and expand the mutational spectrum in these disorders., This work was supported by the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness, Spain and co-funded by European Union (ERDF, “A way to make Europe”) (PI15-01648 and PI18-00612, to G.A.), Regional Ministry of Health and Families of the Autonomous Government of Andalusia (PEER-0501-2019, to G.A.) and the Foundation Isabel Gemio/Foundation Cajasol (FGEMIO-2019-01, to G.A.). The CIBERER is an initiative of the ISCIII, Spanish Ministry of Economy and Competitiveness. EFS is supported by fellowship FI19/00091 from ISCIII and co-funded by ESF, “Investing in your future”. MMS is supported by a fellowship associated with the CTS-1664 project, which has been funded by the Regional Ministry of Economy, Knowledge, Enterprise, and University of the Regional Government of Andalusia.

To describe the clinical presentations and image findings of a patient with foveal hypoplasia.Observational case report of one patient. The clinical presentation of the patient was documented by fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography.A 55-year-old healthy white female with bilateral foveal hypoplasia without nystagmus was presented. There were no signs suggestive of ocular albinism. Absence of foveal depression was noted on both clinical examination and optical coherence tomography. Lack of foveal avascular zone was confirmed on fluorescein angiography and optical coherence tomography angiography.To the best of our knowledge this is the first report of findings in foveal hypoplasia examined by angio-optical coherence tomography. Optical coherence tomography angiography is an easy, rapid, and noninvasive tool that allows imaging of the retinal microvasculature without intravenous dye injection.

Background Partial lamellar sclerouvectomy was designed more than 30 years ago by Jerry and Carol Shields, in order to remove melanomas that involved the ciliary body and/or the choroid, while leaving intact the outer portion of the sclera and the overlying sensory retina [ 1 ]. Methods We present two cases of iris-ciliary body melanoma with different size. The performed surgery was a partial lamellar sclerouvectomy plus iridectomy, complemented by intraoperative juxtalimbar ruthenium-106 brachytherapy. Results Both cases achieved anatomical success without developing chronic ocular hypotony in the postoperative period, an infrequent but possible complication [ 2 ]. Even one of them reached a best-corrected visual acuity of 0.7 after silicone oil removal and intravitreal implant of dexamethasone because of secondary macular edema. The other remains stable with counting fingers vision. In this case, the poor functional outcome might be influenced by larger size and longer evolution of the tumor, as well as the uncontrolled arterial hypertension and older age of the patient. Discussion Intraoperative ophthalmic brachytherapy may have a beneficial effect not only over neoplastic activity [ 2 ], but also over early choroidal detachments. Its pro-fibrotic/hemostatic stimulus should be further examined by comparative studies with larger cohorts, either prospectively or retrospectively. Other protective factors could be the utilization of equine pericardial grafts for covering scleral defects as well as leaving high-density silicone oil. Another key aspect is to maintain low blood pressure levels during these procedures in order to avoid intraocular hemorrhages [ 3 ], especially when the patient exceeds the sixth decade, so the anaesthesiologist will also play a decisive role in the operating room. We prefer to anticipate the likely development of lens opacification after this operation [ 4 ], performing cataract surgery at the beginning and using a Cionni capsular tension ring due to a probable zonular instability. Pars plana vitrectomy would also remove peripheral vitreoretinal tractions and seal the retina preventing a detachment. Conclusion As can be observed during the surgical video, a wide range of complications could occur during a partial lamellar sclerouvectomy. Tackle them ahead of time is crucial to achieve anatomical and functional success.

Purpose Artificial tears only provide transient relief for dry eye. To the best of our knowledge, this is the first study to objectively compare treatment with artificial tears with Keratograph 5M, which allows accurate and objective investigation of dry eye and artificial tear treatment. We aimed to evaluate whether a preservative-free combination of 0.4% hyaluronic acid and 0.2% galactoxyloglucan can improve dry eye using the new topographer, Keratograph 5M. Patients and Methods This prospective longitudinal, single-arm interventional cohort study was performed at a tertiary referral center and involved 20 patients with dry eye (40 eyes). Preservative-free artificial tears were administered every 3 h. The participants underwent clinical and instrumental evaluations at baseline, 15, 30, 60, 90 and 120 min after instillation and 1 week and 1 month after treatment. Baseline values were considered as the controls. All patients were assessed with Keratograph 5M for non-invasive Keratograph first break-up time and non-invasive Keratograph average break-up time, conjunctival hyperemia, and tear meniscus height. Ocular surface staining with fluorescein was evaluated using the slit-lamp and fluorescein break-up time examinations, and the Ocular Surface Disease Index score was recorded for each patient. Results The signs and symptoms improved after 1 month of preservative-free 0.4% hyaluronic acid and 0.2% galactoxyloglucan treatment. There was a significant increase in the non-invasive Keratograph first break-up time and non-invasive Keratograph average break-up time at 15, 30, 60, and 90 min, and 1 week and 1 month (P < 0.05) and a decrease in hyperemia, corneal staining, and Ocular Surface Disease Index scores after 1 week and 1 month (P < 0.05). No treatment-related adverse event was observed. Conclusion A combination of 0.4% hyaluronic acid and 0.2% galactoxyloglucan artificial tears seems effective for treating dry eye. Keratograph 5M can objectively detect these changes during the follow-up period.

[Background] Retinitis Pigmentosa (RP) is a clinically and genetically heterogeneous disorder that results in inherited blindness. Despite the large number of genes identified, only ~ 60% of cases receive a genetic diagnosis using targeted-sequencing. The aim of this study was to design a whole genome sequencing (WGS) based approach to increase the diagnostic yield of complex Retinitis Pigmentosa cases., [Methods] WGS was conducted in three family members, belonging to one large apparent autosomal dominant RP family that remained unsolved by previous studies, using Illumina TruSeq library preparation kit and Illumina HiSeq X platform. Variant annotation, filtering and prioritization were performed using a number of open-access tools and public databases. Sanger sequencing of candidate variants was conducted in the extended family members., [Results] We have developed and optimized an algorithm, based on the combination of different open-access tools, for variant prioritization of WGS data which allowed us to reduce significantly the number of likely causative variants pending to be manually assessed and segregated. Following this algorithm, four heterozygous variants in one autosomal recessive gene (USH2A) were identified, segregating in pairs in the affected members. Additionally, two pathogenic alleles in ADGRV1 and PDZD7 could be contributing to the phenotype in one patient., [Conclusions] The optimization of a diagnostic algorithm for WGS data analysis, accompanied by a hypothesis-free approach, have allowed us to unmask the genetic cause of the disease in one large RP family, as well as to reassign its inheritance pattern which implies differences in the clinical management of these cases. These results contribute to increasing the number of cases with apparently dominant inheritance that carry causal mutations in recessive genes, as well as the possible involvement of various genes in the pathogenesis of RP in one patient. Moreover, our WGS-analysis approach, based on open-access tools, can easily be implemented by other researchers and clinicians to improve the diagnostic yield of additional patients with inherited retinal dystrophies., This work was supported by the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness, Spain and co-funded by European Union (ERDF, “A way to make Europe”) [PI15-01648] and [PI18-00612], CIBERER ACCI [ER16P1AC702/2017], Regional Ministry of Economy, Innovation, Science and Employment of the Autonomous Government of Andalusia [CTS-1664] and Regional Ministry of Health and Families of the Autonomous Government of Andalusia [PEER-0501-2019]. The Foundation Isabel Gemio/Fundación Cajasol. The CIBERER is an initiative of the ISCIII, Spanish Ministry of Economy and Competitiveness. EFS is supported by fellowship FI19/00091 from ISCIII and co-funded by ESF, “Investing in your future”.

[Background/aims] Limbal stem cell deficiency (LSCD) is characterised by a marked decrease in limbal stem cells. It is classified primarily using subjective slit-lamp observations. In vivo confocal microscopy (IVCM) can non-invasively provide objective information on the condition of the limbal niche, the corneal epithelial basal cell density and the corneal sub-basal nerve plexus density (SND). We here used IVCM to evaluate changes in SND to improve LSCD classification. [Methods] We evaluated and classified 38 patients (76 eyes, 44 with LSC and 32 control eyes) using the Rama, López-García and Deng (clinical and confocal) classifications and evaluated the concordance of the confocal and clinical classifications. We constructed a logistic regression model using multivariate analysis to correlate different degrees of conjunctivalisation with IVCM parameters and used receiver operating characteristic (ROC) curve analysis to establish the SND cut-off value with maximum diagnostic sensitivity and specificity. [Results] The classification systems correlated moderately at best (kappa, 0.449). The corneal SND of cases (6469±6295 µm/mm2) was less (p, Iniciativa Andaluza en Terapias Avanzadas (IATA). MC-M, JM-I and ER-d-l-R are members of RETICS OFTARED ’RD16/0008/0010’, financed by the Instituto de Salud Carlos III, as part of the Plan Nacional I+D+i 2013-2016 and cofinanced by the European Union (FEDER/FSE) ’Una manera de hacer Europa’. IATA and RETICS OFTARED have sponsored the translation of this manuscript.

Damage to the retinal pigment epithelium (RPE) in age-related macular degeneration and other diseases results in photoreceptor cell death and blindness. Replacement of RPE is therefore being explored as a therapy for several retinal diseases. To move toward a future personalized autologous transplant approach, we have prepared a biocompatible implant using RPE derived from induced pluripotent stem cells (iPSCs) reprogrammed from a healthy donor's monocytes. The correct positioning of the polarized RPE is essential to fulfill its role and protect photoreceptors from degeneration. Hence, we have used a biocompatible hydrogel matrix of fibrin and agarose that allows the surgical placement of an RPE sheet in the subretinal space, keeping its functional orientation. Our aim was to demonstrate safety and viability of the transplant in preclinical models. Pigs were used to test the feasibility of a regular vitreoretinal surgery. Our results show that this implant is suitable for subretinal transplantation allowing human RPE cells to survive and maintain their phenotype and orientation without any local or systemic adverse events. The ability to transplant the iPSC-derived RPE sheet in its natural orientation will surely increase the chance to obtain a therapeutic effect in future translational studies. In the promising field of cellular therapy for retinal degenerative diseases, a new biomaterial is proposed as a scaffold to grow and surgically introduce a monolayer of retinal pigment epithelial cells into the subretinal space, keeping the orientation of the cells for a proper functional integration of the transplant. The use of induced pluripotent stem cells as the starting material for retinal pigment epithelial cells is intended to advance toward a personalized medicine approach., Study supported by Consejería de Salud, Junta de Andalucía and by ISCIII (Miguel Servet-I, 2015) cofinanced by European Regional Development Fund (ERDF) (CP/00071).

Inherited Retinal Dystrophies are clinically and genetically heterogeneous disorders affecting the photoreceptors. Although NGS has shown to be helpful for the molecular diagnosis of these conditions, some cases remain unsolved. Among these, several individuals harboured monoallelic variants in a recessive gene, suggesting that a comprehensive screening could improve the overall diagnosis. In order to assess the contribution of non-coding variations in a cohort of 29 patients, 25 of them with monoallelic mutations, we performed targeted NGS. The design comprised the entire genomic sequence of three genes (USH2A, ABCA4 and CEP290), the coding exons of 76 genes and two disease-associated intronic regions in OFD1 and PRPF31. As a result, likely causative mutations (8 novel) were identified in 17 probands (diagnostic rate: 58.62%), including two copy-number variations in USH2A (one deletion of exons 22–55 and one duplication of exons 46–47). Possibly damaging deep-intronic mutations were identified in one family, and another with a monoallelic variant harboured causal mutations in a different locus. In conclusion, due to the high prevalence of carriers of IRD mutations and the results obtained here, sequencing entire genes do not seem to be the approach of choice for detecting the second hit in IRD patients with monoallelic variants., This work was supported by Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness, Spain and co-funded by European Union (ERDF/ESF, “Investing in your future”) [PI15-01648], CIBERER ACCI [ER16P1AC702/2017] and Regional Ministry of Economy, Innovation, Science and Employment of the Autonomous Government of Andalusia [CTS-1664]. The CIBERER is an initiative of the ISCIII, Spanish Ministry of Economy and Competitiveness. MM-S is supported by fellowship from Regional Ministry of Economy, Innovation, Science and Employment of the Autonomous Government of Andalusia (CTS-1664).

Lacrimal punctal plugs may prevent the teratogenicity of the treatment used in infectious keratitis. Its use should be strongly considered in these cases.We present the case of a 7-week pregnant patient with Acanthamoeba keratitis.The patient was a contact lens user with photophobia, redness, and intense pain in the right eye that started 2 weeks earlier. Corrected visual acuity was 20/63 (0.5 logMAR). Biomicroscopy revealed a ciliary injection, perineural infiltrates, and corneal edema. Confocal microscopy and culture confirmed the diagnosis of Acanthamoeba keratitis. Prior to treatment with amebicidal eye drops, plugs were implanted in the lacrimal puncta to reduce the risk of drugs' teratogenicity. Three months after initiating amebicidal treatment, a melting ulcer of immunological etiology developed, which was treated with ReGeneraTing Agent eye drops, carboxymethyl glucose polysulfate (Cacicol; Théa, Clermont-Ferrand, France).Lacrimal occlusion with punctal plugs is one of the available options available in cases of pregnant patients to reduce the risk of teratogenicity.

Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy (IRD) characterized ultimately by photoreceptors degeneration. Exhibiting great clinical and genetic heterogeneity, RP can be inherited as an autosomal dominant (ad), autosomal recessive (ar) and X-linked (xl) disorder. Although the relative prevalence of each form varies somewhat between populations, a major proportion (41% in Spain) of patients represent simplex cases (sRP) in which the mode of inheritance is unknown. Molecular genetic diagnostic is crucial, but also challenging, for sRP patients because any of the 81 RP genes identified to date may be causative. Herein, we report the use of a customized targeted gene panel consisting of 68 IRD genes for the molecular characterization of 106 sRP cases. The diagnostic rate was 62.26% (66 of 106) with a proportion of clinical refinements of 30.3%, demonstrating the high efficiency of this genomic approach even for clinically ambiguous cases. The high number of patients diagnosed here has allowed us to study in detail the genetic basis of the sRP. The solved sRP cohort is composed of 62.1% of arRP cases, 24.2% of adRP and 13.6% of xlRP, which implies consequences for counselling of patients and families., This work was supported by Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness, Spain [PI11-02923] and co-funded by European Union (ERDF/ESF, “Investing in your future”) [PI15-01648], CIBERER ACCI [ER14P1AC702/2015], Regional Ministry of Economy, Innovation, Science and Employment of the Autonomous Government of Andalusia (CTS-1664). The CIBERER is an initiative of the ISCIII, Spanish Ministry of Economy and Competitiveness. NB-G is supported by fellowship FI12/00545 from ISCIII and MM-S by fellowship from Regional Ministry of Economy, Innovation, Science and Employment of the Autonomous Government of Andalusia (CTS-1664).

We aimed at reporting the first case of rapidly progressive acute postoperative endophthalmitis after phacoemulsification cataract surgery in an immunocompetent patient caused by Rothia mucilaginosa. An immunocompetent patient manifested endophthalmitis signs 48 hours after an uncomplicated cataract surgery by phacoemulsification. A bacteria of the family Micrococcaceae was cultured in the vitreous biopsy, namely R. mucilaginosa. The patient did not show a favorable clinical response after vitrectomy and systemic, intravitreal, and topical fortified antibiotics. The patient’s eye was very painful, and consequently, it deemed necessary to perform an evisceration. R. mucilaginosa may be an aggressive etiologic agent for postoperative endophthalmitis. Although the isolated R. mucilaginosa was susceptible to empirical treatment, it was impossible to control the infection with standard treatment, probably due to its ability to create a biofilm around the intraocular lens.

Purpose: To evaluate structure and cellular functionality of retinal pigment epithelium (RPE)-choroid grafts after autologous translocation in porcine eyes. Methods: Retinal pigment epithelium-choroid grafts were obtained from the nasal midperiphery donor site and translocated to the central area in 12 pigs (12 eyes). Grafts were placed under the central retina through a retinotomy. Ophthalmoscopic and pathological evaluations were performed immediately (n = 1) and at 15 (n = 3) and 30 (n = 3) days after surgery. Untranslocated nasal RPE-choroid grafts were obtained at time of surgery and used as controls. Specimens were evaluated by standard histology and by immunochemical studies of RPE65, CRALBP and GFAP. Results: Five animals were lost to follow-up owing to surgery or anaesthesia complications. Ophthalmoscopic examination revealed that the grafts remained in place at all time-points studied. Fifteen and thirty days postsurgery, some areas of the transplanted RPE maintained a monolayered structure. Retinal pigment epithelium cells were firmly attached to Bruch’s membrane and predominantly preserved polarity and pigment distribution. However, RPE65, CRALBP and GFAP patterns of expression and distribution were diminished and modified during follow-up. Ophthalmoscopic retinal detachment and proliferative vitreoretinopathy (PVR), confirmed by microscopic evaluation, complicated all cases at 30 days of follow-up. Conclusion: Autologous RPE-choroid grafts survived up to 30 days in porcine eyes. Histological and immunochemical evaluation revealed preserved transplanted RPE cells morphology accompanied by alterations in the immunoreactivity expression of functional proteins, and development of significant PVR. The data presented in this manuscript provide insights into the fate, viability and cellular functionality of the transplanted RPE-choroid graft, serving as foundation for further knowledge and improvement of this technique.

Next-generation sequencing (NGS) has overcome important limitations to the molecular diagnosis of Inherited Retinal Dystrophies (IRD) such as the high clinical and genetic heterogeneity and the overlapping phenotypes. The purpose of this study was the identification of the genetic defect in 32 Spanish families with different forms of IRD. With that aim, we implemented a custom NGS panel comprising 64 IRD-associated genes in our population, and three disease-associated intronic regions. A total of 37 pathogenic mutations (14 novels) were found in 73% of IRD patients ranging from 50% for autosomal dominant cases, 75% for syndromic cases, 83% for autosomal recessive cases, and 100% for X-linked cases. Additionally, unexpected phenotype-genotype correlations were found in 6 probands, which led to the refinement of their clinical diagnoses. Furthermore, intra- and interfamilial phenotypic variability was observed in two cases. Moreover, two cases unsuccessfully analysed by exome sequencing were resolved by applying this panel. Our results demonstrate that this hypothesis-free approach based on frequently mutated, population-specific loci is highly cost-efficient for the routine diagnosis of this heterogeneous condition and allows the unbiased analysis of a miscellaneous cohort. The molecular information found here has aid clinical diagnosis and has improved genetic counselling and patient management., This work was supported by the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness, Spain (PI11-02923), CIBERER ACCI, CDTI FEDER-Innterconecta (EXP00052887/ITC-20111037), Regional Ministry of Economy, Innovation, Science and Employment of the Autonomous Government of Andalusia (CTS-1664) and the Foundation Ramon Areces (CIVP16A1856). The CIBERER is an initiative of the ISCIII, Spanish Ministry of Economy and Competitiveness. NB-G is supported by fellowship FI12/00545 from ISCIII.

Purpose: The aim is to describe the main characteristics of an anterior/posterior segment surgery and how to resolve intraoperative complications. Setting/Venue: The anterior and posterior segment surgical video was created at the Department of Ophthalmology, Virgin Macarena University Hospital, Seville, Spain. Methods: We present the case of a male with Stevens-Johnson syndrome and severe limbal deficiency who needed a Boston type 1 keratoprosthesis, reaching a visual acuity of 0.4 (0.05 before surgery). In the course of follow-up, he developed corneal melting with perforation, immune vitritis, and a large epimacular membrane. We decided to perform a 23-gauge vitrectomy associated with keratoprosthesis exchange. As a consequence of inappropriate anesthesia, the patient woke up during the surgery, provoking a retinal tear besides a choroidal detachment. These damages needed endolaser photocoagulation as well as silicone oil tamponade, forcing us to postpone the exchange. An intravitreal dexamethasone implant was also injected. Two months later, the silicone oil was removed, and the Boston keratoprosthesis was replaced by a new type 1 model with a titanium back plate, which likely improves biocompatibility and retention and may reduce complications such as retroprosthetic membranes and stromal corneal melts. Results: Good anatomical results were achieved, and visual acuity slightly improved to 0.2. Conclusions: Combined anterior and posterior segment surgery represents a great challenge that can improve not only visual acuity but also quality of life in patients with severe diseases such as Stevens-Johnson syndrome.

To report the major intraretinal pathological changes in retinas with proliferative vitreoretinopathy (PVR) and retinal shortening, 13 human retinal samples from postoperative PVR after primary surgery for retinal detachment were immunostained for vimentin, glial fibrillary acidic protein (GFAP), cytokeratins, and CD68. One more sample was studied with electron microscopy. Retinal disorganization, neuronal loss, and gliosis were observed in 12 out of 13 samples, but all 13 were positive for GFAP. Müller cell processes showed different degrees of intermediate filament hyperplasia. CD68-positive cells were present in 11 of 13 retinal samples. Conclusion: A gliotic response plays a major role in retinal shortening in PVR. In addition, the presence of macrophage-like cells in retinal tissues suggests a possible role of these cells in the pathogenesis of this variety of PVR.

Purpose: To compare the cellularity of vitreous samples obtained from patients with rhegmatogenous retinal detachment complicated by proliferative vitreoretinopathy (PVR) and from patients with uncomplicated rhegmatogenous retinal detachment (RD) to detect possible variations in cellularity over time. Methods: One hundred and twenty-five vitreous specimens collected from patients with RD (n = 41) and PVR (n = 84) were processed through direct paraffin embedding and cytospin. Different cell types were identified by light-microscopy (hematoxylin-eosin and Papanicolaou stain) according to their morphologic features, and a scale of cellular density was established for each cell type. Student’s t test was used to analyze differences in the cellularity of RD versus PVR. A quadratic model was used to identify variations in the density of each cellular type in the PVR group, based on its evolution time. Results: During the first months after surgery, more macrophages and fibroblast-like cells were observed in the PVR group, but at other times no differences were found. Conclusions: There are some differences in vitreous cellularity in PVR specimens when compared with RD. Especially relevant could be the large number of macrophages in earlier stages and their constant presence over time in PVR samples. The cytology of vitreous samples may shed light on the chronology of PVR cell pathobiology.

Purpose. To quantify the frequency of visual loss after successful retinal detachment (RD) surgery in macula-on patients in a multicentric, prospective series of RD.Methods. Clinical variables from consecutive macula-on RD patients were collected in a prospective multicentric study. Visual loss was defined as at least a reduction in one line in best corrected visual acuity (VA) with Snellen chart. The series were divided into 4 subgroups: (1) all macula-on eyes (n=357); (2) macula-on patients with visual loss at the third month of follow-up (n=53) which were further subdivided in (3) phakic eyes (n=39); and (4) pseudophakic eyes (n=14).Results. Fifty-three eyes (14.9%) had visual loss three months after surgery (n=39phakic eyes;n=14pseudophakic eyes). There were no statistically significant differences between them regarding their clinical characteristics. Pars plana vitrectomy (PPV) was used in 67.2% of cases, scleral buckle in 57.7%, and scleral explant in 11.9% (36.1% were combined procedures).Conclusions. Around 15% of macula-on RD eyes lose VA after successful surgery. Development of cataracts may be one cause in phakic eyes, but vision loss in pseudophakic eyes could have other explanations such as the effect of released factors produced by retinal ischemia on the macula area. Further investigations are necessary to elucidate this hypothesis.

Purpose To present the different evolution of 2 cases of endophthalmitis caused by Fusarium solani, an aggressive filamentous fungus, depending on the medical and surgical treatment performed. Methods We present 2 cases of endophthalmitis caused by Fusarium solani. Topical, intrastromal, intravitreal, and systemic antifungal treatment (natamycin, voriconazole, amphotericin B) failed in both cases. Corneal perforation took place in one of them, being unsuccessfully treated with cyanoacrylate and several amniotic membrane transplants. It became necessary to perform a hot penetrating keratoplasty (PK) in both patients. The lenses were removed, and the microbiological analysis showed their colonization by Fusarium solani. In one of the cases, a second PK and a more aggressive pars plana vitrectomy (PPV) were performed after corneal recurrence detected by confocal microscopy, as well as the following therapeutic intra- and postoperative maneuvers: anterior chamber washing with povidone-iodine 5% for 1 min; iridectomy of the infiltrated regions; aspiration of the fungal colonies with vitrector; several air/fluid/amphotericin/voriconazole exchanges during PPV; endodiathermy and endophotocoagulation of the chorioretinitis foci; and intrascleral angle injections of voriconazole and amphotericin. Results These were the only cases of endophthalmitis caused by Fusarium attended to at our hospital during the last 10 years. In the case in which PPV was performed without those maneuvers, endophthalmitis rapidly recurred in a more aggressive way, so finally it became necessary to eviscerate the globe. On the other hand, in the patient who underwent PPV with the specific surgical maneuvers and postoperative procedures described above, we could preserve the eye and even a vision of hand motion without an intraocular lens. Conclusions The main objectives of these surgical procedures are to control the fungal infection and to preserve the ocular globe. It is essential to eliminate all ocular structures (iris, lens, vitreous, etc.) affected by this strain of fungus in order to reduce the risk of recurrence. When indicated, early surgery with the appropriate maneuvers detailed above may make an evisceration unnecessary and even recover some visual acuity.

To examine intravitreal silicone oil samples for lipophilic substances, including cholesterol, fatty acids, and derived methyl esters.Clinical interventional case series study.The study included 53 patients (53 eyes; mean age 57.6 years) who underwent removal of intravitreal silicone oil used for intraocular tamponade with pars plana vitrectomy for retinal detachment. The silicone oil was removed 8.3 +/- 5.7 months after pars plana vitrectomy and analyzed using gas chromatography with a flame ionization detector.Cholesterol was present in all samples with a mean concentration of 65 +/- 32.3 microg/ml (95% confidence interval: 56.1 to 73.9 microg/ml). The concentration increased (P.001) with the time of tamponade, and decreased (P = .003) with the age of the patients. Fatty acids along with derived methyl acids were detected in low concentrations in 49 samples (92.5%).Cholesterol and lipophilic acids accumulate in intravitreal silicone oil used in intraocular tamponade.

Purpose: To externally validate the accuracy of previously published formulas for predicting proliferative vitreoretinopathy development after retinal detachment surgery. Methods: Clinical variables from consecutive retinal detachment patients (n = 1,047) were collected from the Retina 1 Project conducted in 17 Spanish and Portuguese centers. These data were used for external validation of four previously published formulas, F1 to F4. Receiver-operating characteristic curves were used to validate the quality of formulas, and measures of discrimination, precision, and calibration were calculated for each. Concordance among the formulas was determined by Cohen kappa index. Results: The areas under the receiver-operating characteristic curves were as follows: F1, 0.5809; F2, 0.5398; F3, 0.5964; and F4, 0.4617. F1 had the highest accuracy, 74.21%. Almost 19% of proliferative vitreoretinopathy cases were correctly classified by F1 compared with 13%, 15%, and 10% for F2, F3, and F4, respectively. There was moderate concordance between F2 and F3 but little between the other formulas. Conclusion: After external validation, none of the formulas were accurate enough for routine clinical use. To increase its usefulness, other factors besides the clinical ones considered here should be incorporated into future formulas for predicting risk of developing proliferative vitreoretinopathy.

Purpose. To analyse variations in the anatomical and functional outcomes and in proliferative vitreoretinopathy (PVR) rate of a prospective multicentric study that was primarily designed for identification of clinical risk factors for PVR. Methods. 1,046 retinal detachment (RD) cases were analysed. Cases were divided into two series based upon variation in PVR rate determined by logistic regression analysis. Series 1 (S1) included RD treated during 2004-2005 (n=481) and Series 2 (S2) during 2006–2008 (n=565). Pre-, intra-, and postoperative characteristics were recorded. Results. There were few differences in the preoperative characteristics. S2 had more vitrectomies and scleral bands and fewer explants and associated cataract extractions than S1. Anatomic reattachment improved from 87.9% to 92.9% in S1 and S2, respectively, (P=0.006). Visual acuity at 3 months ≥20/40 increased from 36.5% of S1 to 44.2% in S2 (P=0.049). PVR rate diminished from 14.1% in S1 to 8.1% in S2 (P=0.002). Centres with higher rates of PVR in S1 showed the greatest reductions in S2. Conclusion. An improvement in anatomical and functional outcome and PVR rate occurred in participating centres cannot be attributed to the learning curve of surgeons. We speculated that it could be an effect of their participation in the study.

PURPOSE To identify the indications and differences in outcomes for adding a scleral buckle (SB) to pars plana vitrectomy (PPV) in a prospective series of rhegmatogenous retinal detachment (RD) by using propensity score matching (PSM) to analyze causal effects in observational studies. METHODS Data were collected from the Retina 1 Project, a prospective, interventional, nonrandomized study of consecutive RDs. Case selection was based upon treatment with PPV or PPV+SB. Surgeons followed personal criteria for the inclusion of SB in the PPV. Propensity score matching corrected for selection biases. Outcomes were assessed by anatomic and visual criteria and the development of proliferative vitreoretinopathy. RESULTS Of 523 patients analyzed, 251 had PPV and 272 had PPV+SB. Surgeons used PPV+SB more frequently in younger patients with RD, in those with posterior or unidentified breaks, in phakic eyes, in eyes with the posterior vitreous attached, and for more extended RDs. Overall single surgery anatomic success rate was 86.4%. Based on PSM, there were no difference in reattachment rates of the PPV group, 86.9%, and the PPV+SB group, 85.93%. The incidence of PVR was similar in both groups, with 8.5% in the PPV group and 10.5% in the PPV+SB group. CONCLUSIONS Data from the Retina 1 Project established the indications for adding SB to PPV in treating primary RD in this series. No anatomic or visual differences between PPV and PPV+SB were found.

Purpose: The aim is to describe the main characteristics of different approaches in vitreomacular traction surgery. Setting/Venue: The video (see www.karger.com/doi/10.1159/ 000442579) about vitreomacular traction surgery was created at the Department of Ophthalmology, Virgin Macarena University Hospital, Seville, Spain. Methods: We present the surgical release of vitreomacular tractions in three different pathologies: (1) idiopathic epimacular membrane; (2) proliferative diabetic retinopathy with long-term hemovitreous, and (3) Coats' disease. Results: Although functional success is less common than anatomical success, we will never be able to improve vision without restoring retinal anatomy. Conclusions: Vitreomacular tractions are perfectly well known by ophthalmologists. However, the method used to release them must be the least aggressive possible in order to avoid retinal tears or macular holes with subsequent visual loss.

J Carlos Pastor1,3, Itziar Fernández2, Jimena Rojas1, Rosa Coco1, Maria R Sanabria1, Enrique Rodríguez-de la Rúa1,3, Diego Sánchez3, Carmen Valverde3, Anna Sala Puigdollers1,31University Institute of Applied Ophthalmobiology (IOBA), Retina Group, 2Ministry of Science and Innovation CIBER-BBN, Statistics Department, 3Clinic University Hospital, University of Valladolid, Valladolid, SpainBackground: Uniform postresidency systems to train medical specialists have not been developed in most European countries. Before developing a framework for such a system, we established the learning and professional profiles of Spanish ophthalmologists dedicated to medical retina and vitreoretina subspecialties.Methods: After identification of presumed subspecialists by experts from different autonomous regions, a self-administered questionnaire was mailed in 2006. A reminder was sent three weeks later. Postal mail was used. Nonresponder bias was determined.Results: Of 492 possible retina subspecialists, 261 replied to the questionnaires. While about 86% received specific retinal training, standardized fellowship programs were uncommon for both medical retina and vitreoretina (around 10%). Of the responders, 24.5% performed only medical retina, 11.8% vitreoretina, and 63.6% both. Most (60.5%) practiced anterior segment surgery, and 78.7% declared skills in vitrectomy.Conclusion: We have developed a database of Spanish ophthalmologists dedicated to retinal pathologies and identified some characteristics of their professional profile. Although most of them have received specific retinal training, standardized mastership programs are still uncommon. These data will be useful in creating a standardized Retina Mastership, an important goal of the European Higher Education Area.Keywords: clinical activity, fellowship, mastership, professional profile, retinologist training

PURPOSE. Machine learning techniques were used to identify which of 14 algorithms best predicts the genetic risk for development of proliferative vitreoretinopathy (PVR) in patients who are experiencing primary rhegmatogenous retinal detachment (RD). METHOD Data from a total of 196 single nucleotide polymorphisms in 30 candidate genes were used. The genotypic profile of 138 patients with PVR following primary rhegmatogenous RD and 312 patients without PVR RD were analyzed. Machine learning techniques were used to develop statistical predictive models. Fourteen models were assessed. Their reproducibility was evaluated by an internal cross-validation method. RESULTS The three best predictive models were the lineal kernel based on the Support Vector Machine (SMV), the radial kernel based on the SVM, and the Random Forest. Accuracy values were 78.4%, 70.3%, and 69.3%, respectively. The more accurate, although complex, algorithm uses 42 SNPs, whereas the simpler one uses only two SNPs, which makes them more suitable for routine diagnostic work. The radial kernel based on SVM uses 10 SNPs. The best individually predictor marker was rs2229094 in the tumor necrosis factor locus. CONCLUSION Genetic variables may be useful to predict the likelihood of the development of PVR. The predictive capabilities of these models are as good as those observed with clinical approaches. These results need external validation to estimate the true predictive capability and select the most appropriate ones for clinical use. © Association for Research in Vision and Ophthalmology.