Optical coherence tomography and fundus autofluorescence in children with infantile nystagmus syndrome and early-onset retinal dystrophy

Background: The purpose of the study was to compare morphological retinal differences in children with infantile nystagmus syndrome (INS) and early-onset retinal dystrophies (EORD) with healthy controls in order to evaluate the diagnostic value of optical coherence tomography (OCT) and fundus autofluorescence (FAF). Material and methods: Twenty-six children (mean age 10.0 years) were ophthalmologically and electrophysiologically diagnosed as INS and EORD. Their SD-OCT and FAF imaging was prospectively performed and compared with 36 controls (mean age 7.2 years). Results: Optical coherence tomography imaging was successfully completed in 17/26 (mean age 9.7 years) and FAF in 15/26 (mean age 11.1 years) children with EORD. OCT imaging was completed in 29/36 (mean age 8.9 years) and FAF in 15/19 (mean age 8.7 years) control children. In all six children with Leber congenital amaurosis (LCA) photoreceptor layer abnormalities were seen in the peripheral retina using SD-OCT, but macular images could not be obtained. In 5/5 children with congenital stationary night blindness (CSNB) retinal thinning was found in all regions except the fovea. 2/6 children with achromatopsia showed ellipsoid zone disruption with macula thinning. In 1/1 child with blue cone monochromatism reduced macular thickness was observed. In 5/5 children with cone-rod dystrophy the outer retinal signal intensity was decreased. In 2/3 children with complete CSNB, slight foveal hypoautofluorescence was indicated. 1/4 children with achromatopsia showed a central hyperautofluorescent ring. In 1/1 child with blue cone monochromatism slight foveal hypoautofluorescence was observed. 2/7 children with cone-rod dystrophy showed a central hyperautofluorescent ring, and additionally in 1/7 a macular hypoautofluorescence in one eye and an additional patch of hyperautofluorescence centrally in the other eye were found. Conclusion: The study demonstrated OCT and FAF as a non-invasive and fast diagnostic tool that defines morphological changes in early-onset retinal dystrophies in young children with nystagmus

OCULAR TOXOPLASMOSIS

Background. Ocular toxoplasmosis is one of the important causes of severe visual loss in young otherwise healthy people. Diagnosis is clinical, supported by laboratory tests. Current evidence about the timing of toxoplasma infection leading to ocular disease suggests, that recurrent toxoplasmic retinochoroiditis is the result of prenatal (congenital) or remote, postnatal (acquired) infection. The timing of infection is rarely exactly known, and retinitis is not only a late manifestation of congenital disease as previously believed. The purpose is to review recent observations regarding ocular toxoplasmosis, and to review our experiences in the treatment of our patients with this illness.Methods. A review of the medical literature about ocular toxoplasmosis, especially regarding pathogenesis, therapy and prevention of the disease.Results. Epidemiological data for toxoplasmosis are various in different parts of the world. The highest rate is in Brasil. In Slovenia the rate is similar like in France or in the Netherlands (at age 40 there is 60% population seropositive). Toxoplasmosis screening in pregnant women is partly performed since 1991 and systematically since 1995 in Slovenia. No retinochorioditis was found in newborns so far. In the pathogenesis there are some several potential sources and routes of infections, that were previously unrecognized. Ocular involvement in cases of acquired infection appears to be more common than believed before. Classical therapy for ocular toxoplasmosis is still most commonly used. In prevention the education of pregnant women, and correct treatment of infected patients is recommended.Conclusions. The time of infection with Toxoplasma gondii and consequential retinochoroiditis is rarely confirmed. Patients with acquired infection after birth are probably more numerous than with congenital disease. As potentially treatable and preventable cause of visual loss these facts must be considered in primary and secondary prevention of the disease.</p

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries

BACKGROUND: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe. METHODS: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries. RESULTS: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease. CONCLUSIONS: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral

VISUAL OUTCOME IN PRETERM INFANTS ANALYSIS OF PRETERM INFANTS BORN IN LJUBLJANA 1990–1999

Background. Improved perinatal care has increased the survival rate of prematurely born infants. An epidemiological fact that 6–18% and more visually impaired children were prematurely born, emphasises the effect of premature birth on both visual function and development. Despite better knowledge on retinopathy of prematurity (ROP) it is stressed not to underestimate refractive errors, strabismus and visual impairment after brain lesions, being more common in preterm babies.Methods. Over 1300 preterm infants with a birth weight of 1500 g or less and gestational age of 30 weeks or less, born in Maternity Hospital of Ljubljana, Slovenia in the period 1990– 1999 were examined according to contemporary paediatricophthalmologic recommendations. At least one year ophthalmologic follow-up (average 3.5 years) of 594 prematurely born infants with high neonatal risk factors for ROP and with general health problems, was performed. Sex, gestational age, birth weight, artificial ventilation, exchange blood transfusion, bronchopulmonary dysplasia, respiratory distress syndrome, apnoea, septicaemia, intraventricular haemorrhage, hyperbilirubinemia were analysed for correlation with ROP and visual impairment.Results. The survival rate of the studied preterm infants was 65–87% (mean 77.3%). ROP stage 1, 2 has developed in 33 children with a birth weight under 900 g and in 10 with a birth weight 900–1200 g (altogether in 8%). ROP stage 3–5 has been registered (with or without plus disease) in 7 children (below 6%). In 6 children cryo or argon laser photocoagulation has been performed and vitreoretinal surgery in 1 child (without functional results). In the studied group altogether 4 children (below 1%) became blind (visual acuity &lt; 0.05), all of them have had septicaemia. Squint has been registered in 6.9% of children, and has correlated with higher refractive error, mostly myopia. Severe optic nerve atrophy has been noticed already in the first year of follow-up in 2% of children, causing visual loss ≤ 0.3. Low gestational age, need for artificial ventilation, septicaemia and at least one exchange transfusion have shown a significant correlation with ROP. Severe asphyxia has been present in 1.4% of the children, severe intraventricular haemorrhage (grade III-IV) in 5.1%, and periventricular leucomalacia in 4.1% of the examined children. Their association with ROP has not been significant, but these variables seem to influence strongly the postretinal visual development.Conclusions. ROP in children born in the Ljubljana region doesn’t seem to be an epidemiological problem, however it is the responsibility of paediatric ophthalmologists to organise screening and therapy programmes for ROP and to follow up the preterm infants’ visual development, with a special attention to increasing postretinal visual impairment, refractive errors and amblyopia.</p

Seroprevalence of Toxocara antibodies among patients suspected of ocular toxocariasis in Slovenia

Ocular toxocariasis named also ocular larva migrans is caused by larvae of the roundworm Toxocara spp. The purpose of this study was to find out the seroprevalence of Toxocara antibodies in patients suspected of ocular toxocariasis. Between January 2001 and December 2003, sera from 239 ocular patients, aged 3 to 80 years, were examined by ELISA and confirmed by Western blot test. Out of the 239 patients, 172 (72%) were seronegative and 67 (28%) were Toxocara seropositive; 95% CI (22-34%). The median age of Toxocara seropositive patients was 37.6 years. There was no significant difference in the number of Toxocara positive sera between the younger age group (≤14 years) and the older age group (>14 years), p>0.05. A high rate of Toxocara seropositivity in ocular patients should alert the ophthalmologists in Slovenia to include toxocariasis in the differential diagnosis of eye diseases more frequently

Global Retinoblastoma Presentation and Analysis by National Income Level

This cross-sectional analysis reports the retinoblastoma stage at diagnosis across the world during a single year, investigates associations between clinical variables and national income level, and investigates risk factors for advanced disease at diagnosis. Key PointsQuestionIs the income level of a country of residence associated with the clinical stage of presentation of patients with retinoblastoma? FindingsIn this cross-sectional analysis that included 4351 patients with newly diagnosed retinoblastoma, approximately half of all new retinoblastoma cases worldwide in 2017, 49.1\% of patients from low-income countries had extraocular tumor at time of diagnosis compared with 1.5\% of patients from high-income countries. MeaningThe clinical stage of presentation of retinoblastoma, which has a major influence on survival, significantly differs among patients from low-income and high-income countries, which may warrant intervention on national and international levels. ImportanceEarly diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. ObjectivesTo report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and ParticipantsA total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and MeasuresAge at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. ResultsThe cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4\%) were female. Most patients (n=3685 {[}84.7\%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n=2638 {[}62.8\%]), followed by strabismus (n=429 {[}10.2\%]) and proptosis (n=309 {[}7.4\%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5\%) patients having intraocular retinoblastoma and 2 (0.3\%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1\%) having extraocular retinoblastoma and 94 of 498 (18.9\%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 {[}95\% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 {[}95\% CI, 4.30-7.68]). Conclusions and RelevanceThis study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs