The homozygous R504C mutation in MTO1 gene is responsible for ONCE syndrome.

We report clinical and biochemical finding from three unrelated patients presenting ONCE (Optic Neuropathy, Cardiomyopathy and Encephalopathy with lactic acidosis and combined oxidative phosphorylation deficiency) syndrome. Whole-exome sequencing (WES) of the three patients and the healthy sister of one of them was used to identify the carry gene. Clinical and biochemical findings were used to filter variants, and molecular, in silico and genetic studies were performed to characterize the candidate variants. Mitochondrial DNA (mtDNA) defects involving mutations, deletions or depletion were discarded, whereas WES uncovered a double homozygous mutation in the MTO1 gene (NM_001123226:c.1510C>T, p.R504C, and c.1669G>A, p.V557M) in two of the patients and the homozygous mutation p.R504C in the other. Therefore, our data confirm p.R504C as pathogenic mutation responsible of ONCE syndrome, and p.V557M as a rare polymorphic variant.

Ophthalmological manifestations in 6 patients diagnosed with Williams-Beuren syndrome and literature review.

Medical history of 6 patients diagnosed with Williams-Beuren Syndrome (SWB) in pediatric age was revised. All the patients presented characteristic elf facies and cardiovascular abnormalities. All presented good visual acuity, except one case of unilateral amblyopia. The most frequent refractive error was hyperopia (n = 6; 100%) and astigmatism (n = 5; 83.3%). Ocular motility alterations were found in 2 patients (1 case of exophoria with hyperfunction of right inferior oblique and another of congenital endotropia with bilateral hyperfunction of inferior oblique). On the cognitive function, 66.7% (n = 4) had visoperceptive disorders. Other findings were epicanthus (n = 6; 100%) and congenital obstruction of the nasolacrimal duct with unilateral epiphora (n = 1; 16.7%). SWB is a rare disorder with complex ophthalmological and systemic manifestations. For this reason, ophthalmological follow-up of these children is recommended.

Septo-optic dysplasia: Ophthalmological abnormalities in a series of 5 cases.

Septo-optic dysplasia (SOD) is a rare congenital condition of unknown cause, with a characteristic triad that includes optic nerve hypoplasia, pituitary function abnormalities and midline brain defects, in addition to a broad spectrum of symptoms and associations. A total of five clinical cases are presented, four of which met the complete classic triad. All of them showed a wide variety of ophthalmological, endocrinological and neurological alterations. Within the ophthalmological spectrum of SOD, papillary hypoplasia and ocular motility alterations (nystagmus, strabismus) stand out. Other less frequent ones may also appear, such as pupillary alterations, microphthalmia and coloboma. Given the suspicion of SOD, brain MRI scan should be performed, as well as consultation with the paediatric department in order to complete the study and indicate, if necessary, systemic treatment.

Prematurity: A medical history of obligatory consideration when assessing the retinal ganglion cell complex.

INTRODUCTION: Premature children birth and survival is becoming more frequent due to the improvement in obstetric and neonatal care. This makes it increasingly common to find patients with history of preterm birth in ophthalmology clinics, both in pediatric and adult ages. Premature birth can lead to ocular structural changes, being possible to affect the ganglion cell complex (GCC), among other structures, which can be studied using optical coherence tomography. MATERIALS AND METHODS: To carry out a bibliographic review of the studies that analyze GCC in patients with a history of prematurity compared with patients born at term. RESULTS: Several studies that analyze GCC in patients with a history of prematurity are referenced and their results are studied. CONCLUSIONS: In our clinical practice, knowing the history of prematurity is fundamental in the assessment of GCC measured by optical coherence tomography, since this layer is different in the patients with a history of prematurity compared to patients born at term.

Bilateral microphthalmos with bilateral orbital cysts: individualising the treatment according to the visual potential. A case report. / Microftalmia bilateral asociada con quistes orbitarios. Manejo individualizado según el potencial visual. Reporte de caso clínico.

The case is presented of a 3-month-old infant diagnosed with microphthalmos and orbital cysts. Magnetic Resonance Imaging revealed a bilateral microphthalmia with a moderate right cyst and a severe left cyst. Visual potential of the right eye was uncertain. Non-surgical treatment was decided. At the age of 2 years old, physical examination showed a significant decrease of the cysts and visual acuity of hand movements due to the residual vision of his right eye. Microphthalmos with orbital cyst is a rare congenital anomaly. Cysts tend to enlarge with time. At the moment, no standard protocol for the management of this pathology has been described. Unlike in our patient, visual acuity in these patients is usually of no-light perception. The observation could be an alternative in severe cases, since there is a possibility of spontaneous reduction, displacement, or regression of the cysts.

Paediatric optical coherence tomography normative databases: A real need. / Bases de datos normativas en edad pediátrica para tomografía de coherencia óptica: una clara necesidad.

INTRODUCTION: Optical coherence tomography (OCT) has become an essential tool in paediatric ophthalmology. However, none of the currently available OCT devices include any kind of normative database for the paediatric population, which can lead to important interpretation errors. OBJECTIVE: To review the paediatric OCT normative databases. MATERIAL AND METHODS: The applications and implications of the use of paediatric OCT normative databases are reviewed. RESULTS: The paediatric normative databases that have been published so far in scientific literature with different OCT devices for Spanish and European population are presented. CONCLUSIONS: The knowledge and interpretation of paediatric OCT normative databases in our daily clinical practice is crucial in order for the correct interpretation of OCT thickness maps.

[Retinopathy of prematurity screening in Spanish neonatal units]. / Cribado de la retinopatía de la prematuridad en las unidades neonatales españolas.

INTRODUCTION: A wide variety of retinopathy of prematurity (ROP) screening criteria exists in the different hospitals. In 1988, the benefits of cryotherapy treatment in severe ROP cases were demonstrated, and since then, some scientific societies have made recommendations on the screening and treatment of ROP. Within the Spanish scientific community, there are no specific recommendations on screening, diagnosis or treatment. OBJECTIVES: To describe the criteria used in the screening of retinopathy in premature newborns by those Spanish hospitals caring for babies with birth weights below 1,500 g. MATERIAL AND METHOD: A cross-sectional study was performed based on a 50 question questionnaire on screening criteria and other related issues. This questionnaire was sent to those public and private neonatal units in Spain caring for babies with birth weights below 1,500 grams. The questionnaire was sent and returned between January 2002 and May 2003. RESULTS: Units in all of the 17 autonomous communities and both autonomous cities in territorial Spain (Ceuta and Melilla) responded. There was a 90% response rate. All the participating hospitals perform ROP screening. Only 62.9% of the hospitals follow a written protocol on screening. A large majority of hospitals (79.8%) perform a retinal eye examination on all newborns below 1500 g at birth. Half of the hospitals included in the study, 51.6%, determine the cut-off point for performing the screening at 32 weeks of gestational age. Around 73% of the hospitals include the administering of oxygen supplements to premature babies as part of the criteria for screening, regardless of the babies' weight and gestational age. Weight, gestational age and oxygen are the only criteria used in 51% of the units. That all hospitals in Spain should establish some screening criteria was suggested by 90% of the responses. Only 10% use analgesia or sedation, other than topical, when examining the retina. CONCLUSIONS: Even though all the hospitals participating in the study screen for ROP, there is little agreement on which criteria should be followed when screening and on other aspects related to its practice.

[Pediatric cataracts: epidemiology and diagnosis. Retrospective review of 79 cases]. / Cataratas pediátricas: estudio epidemiológico y diagnóstico. Análisis retrospectivo de 79 casos.

PURPOSE: To determine the epidemiology, diagnosis and treatment features in a group of pediatric patients with cataracts treated at our hospital. The aim was to improve the visual prognosis in these patients. METHODS: 79 children with cataracts were reviewed retrospectively during an 18 year period (1986-2004). This involved patients with congenital cataracts and those who acquired them later. Most of the latter group had a traumatic etiology (90%). RESULTS: The etiology of most cataracts was idiopathic (68%) for the congenital group and traumatic (90%) for the acquired group. Congenital cataracts were frequently nuclear in type (31%) with 56% being bilateral. 27% of the congenital group were associated with dysmorphic eye features, the most frequent being microphthalmos. The most frequent presenting feature was leucokoria, seen in 44% of patients. 75% of congenital cataracts were diagnosed within one month of clinical manifestation. 58% of the congenital cataracts were treated by surgery and 50% of these were performed within one month of the diagnosis. 90% of the acquired cataracts were treated surgically, and 95% of these were performed less than one month after diagnosis. CONCLUSIONS: We attained a prompt diagnosis and treatment in a high percentage of cases. Prompt diagnosis and treatment will determine the visual prognosis of these patients. We must continue trying to shorten this period of time in order that all children with this condition are diagnosed and treated urgently and efficiently.

Comparative study of RetCamRetCam II vs. binocular ophthalmoscopy in a screening program for retinopathy of prematurity.

OBJECTIVE: To determine the performance of RetCam vs. binocular ophthalmoscopy (BIO) in a screening program for retinopathy of prematurity (ROP). METHODS: Observational comparative study with prospective data collection. Examinations with RetCam (n=169) were performed on 83 infants included in a screening program for ROP and stored for analysis at a later stage. An experienced ophthalmologist examined the ocular fundus with binocular indirect ophthalmoscopy (BIO). The RetCam images were assessed for the presence of ROP, zone, grade, and presence of plus disease. RetCam and BIO data were compared by visually to estimate sensitivity, specificity, positive (VPP) and negative (VPN) predictive values. RESULTS: ROP disease was detected in 108 eyes with BIO, and in 74 with RetCam. Out of 306 eyes examined with RetCam, false negative results were found in 34 eyes, with no false positives. Sensitivity of RetCam exam vs. BIO was 0.68, and specificity was 0.99. Positive predictive value was 0.93 and negative predictive value was 0.85. All 34 ROP cases not detected with RetCam were in zone III or outer zone II. They were all mild and regressed spontaneously. No threshold ROP was missed with RetCam. CONCLUSION: Binocular indirect ophthalmoscopy is the reference method for the diagnosis of ROP. RetCam may be used as an alternative for ROP screening.

Screening program for retinopathy of prematurity in Spain.

OBJECTIVE: To prepare a retinopathy of prematurity (ROP) screening program as agreed by most of Spanish ophthalmologists dedicated to this topic. MATERIALS AND METHODS: A draft of the protocol was produced taking into account the experience of the participants and current publications. This draft was corrected by all the ophthalmologists participating in the project and the final document produced was agreed by all of them. RESULTS: We present general guidelines to help in the screening of ROP, including treatment criteria, treatment methods, and a calendar of action. CONCLUSIONS: It is important to have a common working protocol in the screening of ROP to improve the action and to avoid mistakes. Although individual Hospitals may adapt the protocol to their daily activity, it is recommended that there is a minimal working protocol agreed by most of professionals dedicated to pediatric ophthalmology in Spain.

[A protocol for the treatment of retinopathy of prematurity in Spain]. / Protocolo de tratamiento de la retinopatía del prematuro en España.

OBJECTIVE: To prepare a protocol for the treatment of retinopathy of prematurity (ROP) agreed by the majority of Spanish ophthalmologists dedicated to this topic. MATERIAL AND METHOD: A draft of the protocol was produced taking into account the experience of the participants and up to date publications. This draft was corrected by all the ophthalmologists participating in the project, and the final document was agreed by all of them. RESULTS: We present general guidelines as an aid for the treatment of ROP, including treatment criteria, treatment methods, a calendar of action, and follow-up. CONCLUSIONS: It is important to have a common working protocol for the treatment of ROP to improve care and to avoid mistakes. Although individual Hospitals may adapt the protocol to their daily activity, it is recommended that there is a minimal working protocol agreed by most of professionals dedicated to pediatric ophthalmology in Spain.

[Intermediate results on the use of drainage devices for paediatric glaucoma]. / Resultados a medio plazo de dispositvos de drenaje para glaucoma en pacientes pediátricos.

PURPOSE: To evaluate the results and long-term complications of glaucoma drainage devices (GDD) in paediatric patients (0-15 years). METHODS: Retrospective cohort study was conducted on 17 implanted glaucoma drainage devices from July 1994 to April 2007 in 14 patients (17 eyes). In two patients (3 eyes) a Molteno GDD (MGDD) was implanted, and in 12 patients (14 eyes) an Ahmed GDD (AGDD) was used. We studied the demographic and glaucoma related patient data, as well as the probability of surgical success. The time which intraocular pressure (IOP) was controlled and the postoperative complications were also studied. RESULTS: Of the fourteen patients, 9 (64.28%) showed congenital glaucoma, and 5 (35.71%) aphakic glaucoma. The pre-aqueous drainage device median IOP was 29.82 mmHg (SD: 6.98), and 14.05 mmHg (SD: 7.57) postoperative. The median follow-up was 3.14 years (3 months-8.3 years). Success of aqueous drainage device was defined as an IOP less than 21 mmHg with or without medication on the last two follow-up visits, and without severe complications or further glaucoma surgery. Using a Kaplan Meier analysis there was success in 76%, 63% and 55% at the six months, 1-3 years and 4-8 years respectively. The GDD was a failure in 41.17%. CONCLUSIONS: GDDs are a good surgery option for refractory paediatric glaucoma when other surgery procedures have failed or have bad prognosti.

[Congenital cataracts: complications and functional results according to different surgical techniques]. / Cataratas congénitas: complicaciones y resultados funcionales según diferentes técnicas quirúrgicas.

PURPOSE: To evaluate visual results, refractive error and complications in a series of congenital cataracts treated with different surgical techniques. METHODS: Retrospective review of 51 eyes with congenital cataracts which were surgically treated between 1989 and 2005. Eleven were unilateral cataracts and 40 were bilateral cataracts. Thirty-three eyes were treated with a primary intraocular lens (IOL) and 18 were aphakic eyes. RESULTS: The best outcomes were observed in bilateral cataracts and in those that received early primary IOL. Three eyes achieved 0.8-1, two eyes achieved 0.6-0.7. All of them were eyes with primary IOL. Seventeen percent of unilateral cataracts and 23.8% of bilateral cataracts achieved 0.4 or better. The most serious complication was visual axis opacification (VAO), 27 of 51 eyes developed VAO. Fifty percent of eyes with primary IOL and 63% of aphakic eyes developed VAO. The VAO developed sooner in the IOL group (6.5 months on average). There was a high myopic shift in 3 eyes. There was a significantly greater myopic shift in the unilateral cases. CONCLUSIONS: The best acuities were achieved in the eyes which had been treated with early primary IOL, but they had a higher rate of complications (VAO), thus requiring reoperation. Final refraction in the unilateral group was significantly more myopic than in the bilateral group.

Multiple evanescent white dot syndrome.

The condition of a 45-year-old woman with diminished visual acuity, multiple yellowish-white dots distributed in the paramacular area, and macular granularity OD was diagnosed as multiple evanescent white dot syndrome. We reviewed the literature and compared our findings with those of the previously reported cases. A differential diagnosis with other entities was also made.

[Impact of new eligibility criteria on a screening program for retinopathy of prematurity. one-year evaluation]. / Impacto de los nuevos criterios de cribado para la retinopatía de la prematuridad. Un año de experiencia.

OBJECTIVE: To evaluate, in clinical and economical terms, a screening program for retinopathy of prematurity 1 year after implementing new eligibility criteria. METHOD: New criteria to safely reduce the number of newborn infants screened without missing any stage 3 retinopathies of prematurity were established after reviewing the clinical information from the 1991-1998 screening program. In 1999 the infants were screened according to the new eligibility criteria. The absolute and relative reduction in the number of patients requiring screening was determined by comparing the implementation of the new eligibility criteria with the previous criteria. Criteria 1991-1998: a) Birth weight 1,500 g or gestational age 33 weeks; and b) gestational age 34-36 weeks with exposure to supplemental oxygen for at least 24 h. New criteria 1999: a) Birth weight 1,250 g or gestational age 30 weeks; and b) infants with birth weight > 1,250 g or gestational age > 30 weeks with very serious neonatal medical problems according to the neonatologist. RESULTS: In 1999, 244 patients would have been screened with the 1991-1998 criteria. Applying the new 1999 criteria, only 72 patients were screened. The number of examinations saved was 369 and the cost of the program decreased by 30,000 euros. CONCLUSIONS: The new eligibility criteria for retinopathy of prematurity screening has reduced the number of patients screened by 70 %. To ensure inclusion of all newborn infants at risk of developing the disease and to minimize the number of screened infants and cost of the program, screening strategies can be tailored to health centers' specific characteristics.