Morning glory disc anomaly in childhood - a population-based study.

PURPOSE: To report prevalence, ocular characteristics and coexisting neurological, behavioural, somatic and neuroradiological abnormalities in children and adolescents with morning glory disc anomaly (MGDA). METHODS: In a cross-sectional population-based study, 12 patients with MGDA, aged 2-20 years, were identified. All 12 agreed to ophthalmological assessments including visual functions, refraction, fundus photography, optical coherence tomography (OCT) and ocular motor score (OMS). Neurological examinations and behavioural/developmental screening were carried out. Data from previous or new neuroradiological investigations were collected. RESULTS: The prevalence of MGDA was 2.6/100 000. MGDA was unilateral in 11/12 patients with a best-corrected visual acuity (BCVA) in the MGDA eye ranging from hand motion to 0.65 (median 0.06). Severe microphthalmus prevented unilaterality to be determined in one adolescent. All patients had a binocular BCVA of ≥0.5. OMS showed abnormalities in pupil response, vestibulo-ocular reflex, stereo visual acuity, strabismus and convergence. OCT revealed peripapillary or macular oedema in 5/8 patients and foveal aplasia in 3/8 patients. Three patients had extensive capillary hemangiomas, of which one had PHACES syndrome and one had additional cerebrovascular anomalies and corpus callosum agenesis. Neuroradiology showed craniovascular anomalies in two patients. Neurology was mostly normal. Behavioural/developmental screening showed attention deficit hyperactivity disorder in one patient. CONCLUSIONS: The prevalence data, previously not reported, of morning glory disc anomaly was 2.6/100 000. Coexisting retinal peripapillary or macular oedema was common, as were cerebral abnormalities and/or cutaneous vascular malformations. The associated findings may not be discovered through routine ophthalmological examination why OCT and neuroimaging are called for.

Recurrence of Susac Syndrome following 23 Years of Remission.

Susac syndrome is an autoimmune microangiopathy affecting the brain, retina and inner ear (cochlea and semicircular canals), leading to encephalopathy, branch retinal artery occlusions (BRAOs) and asymmetric neurosensory hearing loss, respectively. The natural history and long-term prognosis are variable as the disease has been shown to be monophasic and self-limiting, polycyclic or chronic continuous. We describe a 35-year-old woman who presented with a sudden hearing loss in the left ear in the 37th week of her second pregnancy. She subsequently developed BRAO in the right eye 2.5 months after having given birth. MRI findings included round lesions in the corpus callosum which are pathognomonic for Susac syndrome. Previous patient records documented encephalopathy, sudden deafness of the right ear and visual field defects in the left eye at the age of 12, followed by permanent hearing and visual defects. We expand on the variability in the course of Susac syndrome as recurrence may occur after as long as 23 years. Cases of monophasic self-limiting Susac syndrome may in fact turn polycyclic with an interval of more than 2 decades between the bouts of the disease. In these cases, suspecting the development of exacerbation early is important in order to start the treatment promptly.

'Congenital' nystagmus may hide various ophthalmic diagnoses.

PURPOSE: To investigate whether patients registered at a low-vision centre with 'nystagmus' had any underlying, but so far unknown, ophthalmic diagnosis. METHODS: All patients registered at the low-vision centre of Uppsala county with nystagmus as their major diagnosis were identified. Their medical records were studied to exclude those with other general diagnoses that could explain the nystagmus. The remaining group of patients underwent an ophthalmic examination, refraction and optical coherence tomography (OCT). Electroretinogram and genetic analyses were performed when indicated. RESULTS: Sixty-two patients with nystagmus as their main diagnosis were registered at the low-vision centre, Uppsala, and 43 of them had a major diagnosis other than nystagmus. Nystagmus was the major diagnosis in 19 patients, 15 of whom, aged 6-76 years, participated in the study. Two of the patients had foveal hypoplasia and albinism, four a seemingly isolated foveal hypoplasia, three achromatopsia, one rod-cone dystrophy, one degenerative high myopia, and two could not be evaluated. Only two patients appeared to have 'congenital' nystagmus. Eleven of the patients underwent a comprehensive genetic investigation of the PAX 6 gene. In addition, four of the patients were analysed for mutations in FOXC1 and PITX2 and one in FRMD7. No mutations were found in any of the patients analysed. CONCLUSION: The study illustrates that many patients in our study group with nystagmus had underlying ophthalmic diagnoses. Early diagnosis is important to facilitate habilitation and to provide genetic counselling and, in the future, possibly also gene therapy.

Retinal nerve fibre layer thickness in school-aged prematurely-born children compared to children born at term.

AIM: To investigate the retinal nerve fibre layer (RNFL) with optical coherent tomography (OCT) in prematurely-born children. METHODS: 62 children born with a gestational age of ≤32 weeks, and a control group of 54 children born at term with normal birth weight (BW) were included in the study. 28 of the preterm children had retinopathy of prematurity (ROP) in the neonatal period; eight of them had severe ROP (stages 3-4). RNFL thickness was measured with Stratus OCT 3. Mean age at examination was 8.6 years in the preterm children and 10.1 years in the control group. RESULTS: There was a significant difference between the children born preterm and those born at term, regarding RNFL thickness in the superior (right eye (RE), p=0.043; left eye (LE), p=0.048) and the nasal quadrants (RE, p=0.006; LE, p<0.001), as well as average RNFL thickness (RE, p=0.016; LE, p=0.029). This difference was caused by the thinner RNFL in children with previous severe ROP (stages 3 and 4). Within the preterm group, the average RNFL thickness increased with larger BW (RE, p=0.050; LE, p=0.028), but there was no correlation with gestational age at birth. CONCLUSION: The RNFL was reduced in prematurely-born children with severe ROP when compared to children born at term. It is hypothesised that severe retinopathy as well as ablation of the retina with laser treatment or cryotherapy may affect the axons of the ganglion cells and thus reduce RNFL thickness. Prematurely-born children with low BW had a thinner RNFL, suggesting a negative effect of low birth weight on neural development.

Is quantitative spectral-domain superior to time-domain optical coherence tomography (OCT) in eyes with age-related macular degeneration?

PURPOSE: The aim of this study was to determine the variability of macular map measurements, for two generations of optical coherence tomography (OCT) instruments, in eyes with wet age related macular degeneration (AMD) and low visual acuity. METHODS: Patients were examined with Stratus OCT and Cirrus HD-OCT. The macular thickness was assessed with the 'macular thickness map scan' and 'fast protocol' in Stratus and with the 512 × 128 and 200 × 200 cube protocols in Cirrus OCT. Two measurements were taken one directly after the other, at the first visit to analyse repeatability. Approximately 1 week later, a third measurement was taken to analyse reproducibility. In Cirrus OCT, a manual correction of foveal location was also performed. Repeatability and reproducibility were calculated as a coefficient of variance (CoV) and a coefficient of repeatability/reproducibility. RESULTS: Repeatability for central macular thickness (expressed as CoV) was about three per cent for all protocols, and the coefficient of repeatability between 34 and 54 µm. Reproducibility (also expressed as CoV) was between four to seven per cent and coefficient of repeatability between 64 and 89 µm. After manual adjustment of foveal location in Cirrus OCT, the coefficient of repeatability improved to 12-18 µm, and the coefficient of reproducibility to 44-47 µm. CONCLUSIONS: In eyes affected by wet AMD, there were small differences in repeatability and reproducibility when comparing quantitative maps in Stratus and Cirrus OCT. However, when the software for manual correction of foveal position in Cirrus OCT was used, the variability decreased markedly, and the repeatability was close to what had been reported in normal eyes, demonstrating a significant, potential advantage of spectral-domain over time-domain OCT.

Macular edema and visual outcome following cataract surgery in patients with diabetic retinopathy and controls.

BACKGROUND: Cystoid macular edema (CME) is a well-known complication after cataract surgery, and diabetic retinopathy is reported to be an important risk factor for impaired visual recovery. In this prospective study, we compared visual outcome 6 months after surgery in eyes with moderate retinopathy and no previous ME with a control group, and observed the incidence of ME seen on fluorescein angiography (FA) and optical coherence tomography (OCT). METHODS: Thirty-four patients with type-2 diabetes and 35 controls were enrolled. Best-corrected visual acuity (VA) letters ETDRS was measured pre-op, at day 7, week 6 and month 6. FA performed pre-op and at week 6 was divided into three leakage patterns. OCT performed pre-op, at week 6 and month 6 was qualitatively divided into three types. Macular thickness was measured in three circular fields (central subfield, inner and outer circle) from the macular maps. RESULTS: There was no statistically significant difference in VA before surgery, at day 7 or at 6 months, but at 6 weeks there was a significant difference with lower VA in the diabetic group. Six percent of control and 12% of diabetic eyes developed a clinical CME defined as a loss of >5 letters between day 7 and week 6. Incidence of FA leakage was 23% in control and 76% in diabetic eyes. At 6 weeks, 20% of control and 44% of the diabetic eyes had qualitative changes on OCT. A statistically significant increase in thickness was observed for all three macular areas in both groups, part of it remaining at 6 months. There were, however, no differences in central macular thickness between the groups at any visit. Retinal thickening had poor correlation with VA. CONCLUSION: The final visual outcome in eyes with mild to moderate retinopathy, without previous ME, is as good as in normal eyes, but an increased frequency of macular changes may protract recovery of full vision. Changes on OCT or FA are often seen without any obvious effect on VA. OCT is as good as FA at detecting a clinical CME, and is the technique recommended for follow-up before FA is considered.

Retinal nerve fibre layer thickness in full-term children assessed with Heidelberg retinal tomography and optical coherence tomography: normal values and interocular asymmetry.

PURPOSE: This study aimed to investigate normal values and interocular differences in retinal nerve fibre layer (RNFL) thickness, using optical coherence tomography (OCT) and Heidelberg retinal tomography (HRT), in 5-16-year-old children born at full-term with normal birthweights. METHODS: Fifty-six children with normal visual acuity and refraction were examined with Stratus OCT and HRT. Three examinations were performed in each eye. One eye in each child was randomized for analyses of normal values. Findings in 54 eyes were evaluated. Mean values of RNFL thickness were calculated. Coefficients of variance and intraclass correlations were calculated. The correlation between right and left eyes and the limits of difference were determined for both methods. RESULTS: Mean RNFL thickness was 98.4 µm (standard deviation [SD] 7.88 µm) assessed with OCT and 213.0 µm (SD 54.0 µm) assessed with HRT. No correlations between age or gender and RNFL thickness were found. The coefficients of variance were 2.9% and 5.6% for OCT and HRT, respectively, and intraclass correlations were 0.85 and 0.88, respectively. The limits of difference between the two eyes ranged from -9 µm to 9 µm with OCT and from -109 µm to 87 µm with HRT. CONCLUSIONS: Both OCT and HRT can be used in children aged 5-16 years, but OCT provides less variability in determinations of RNFL thickness, both in repeated examinations of the same eye and in comparisons between the two eyes. The present study provides values for normal RNFL thickness in healthy children which can be used to make comparisons with values in children with optic nerve diseases.

Central macular thickness is correlated with gestational age at birth in prematurely born children.

BACKGROUND/AIM: Previous studies have revealed various subnormal visual functions in prematurely born children. The present study aimed to determine the retinal macular thickness in prematurely born children and compare with children born at term. METHODS: The eyes of 65 prematurely born children aged 5-16 years were examined with Stratus optical coherence tomography (OCT) 3, and the results were compared with those of 55 children born at term. The retinal macular thickness in the nine EDTRS macular areas (A1-A9), the foveal minimum and the total macular volume were determined. RESULTS: The central macular thickness (A1 and foveal minimum) was significantly thicker in the prematurely born children than in those born at term. There was no correlation between macular thickness and visual acuity or refraction. Children with previous retinopathy of prematurity (ROP) had significantly thicker central maculae than those without it. Prematurely born children without previous ROP had significantly thicker central maculae than the control group. Multiple regression analyses showed that gestational age at birth was the only risk factor for a thick central macula. CONCLUSION: Prematurely born children had thicker central maculae than those born at term. Regardless of ROP, the degree of prematurity was the most important risk factor for abnormal foveal development.

Optical coherence tomography is helpful in the diagnosis of foveal hypoplasia.

PURPOSE: To investigate whether optical coherence tomography (OCT) is helpful in the diagnosis of foveal hypoplasia in children. METHODS: Children with albinism and aniridia were examined with Stratus OCT 3 software 4.0.1 (Carl Zeiss Meditec, Dublin, California, USA). A qualitative examination of the macular area was performed with a 128 A-scans/second-single-scan. Macular thickness was measured quantitatively with an automatic fast macular map protocol. The average thickness/volume of the macula was presented as numerical values and as a false colour code in nine modified early treatment of diabetic retinopathy study (ETDRS) areas (A1-A9). A previously collected control group of children was used for comparison. RESULTS: Macular thickness in 13 children with albinism and three children with aniridia was measured with OCT. Comparison with healthy children in the same population was performed. Patients with albinism and aniridia had significantly thicker central macula (A1) and foveola than children in the control group. CONCLUSION: OCT was found to be useful in the diagnosis of foveal hypoplasia in children.

SPG11 mutations cause Kjellin syndrome, a hereditary spastic paraplegia with thin corpus callosum and central retinal degeneration.

Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is genetically heterogenous and approximately 35% of patients carry mutations in either of the SPG11 or SPG15 genes. Disease onset is during the first three decades of life with spastic paraplegia and mental impairment. Peripheral neuropathy and amyotrophy may occur. Kjellin syndrome is characterized by central retinal degeneration in addition to ARHSP-TCC and the disease is associated with mutations in the SPG15 gene. We identified five patients in four unrelated kindreds with spastic paraplegia and mental impairment. Magnetic resonance imaging revealed TCC, atrophy elsewhere in the brain and increased T2 signal intensity in the periventricular white matter. Probands from the four kindreds were screened for mutations in the SPG11 gene. All patients were found homozygous or compound heterozygous for truncating SPG11 mutations of which four are reported for the first time. Ophthalmological investigations revealed that the four index cases have central retinal degeneration consistent with Kjellin syndrome. PET examinations with N-[11C-methyl]-L-deuterodeprenyl (DED) and fluor-18 2-fluorodeoxyglucose (FDG) were performed in two patients with Kjellin syndrome. We observed a reduced glucose uptake in the thalami, anterior cingulum, and sensorimotor cortex indicating neuronal loss, and an increased DED binding in the thalami and pons which suggests astrogliosis. From our results we extend the SPG11 associated phenotype to comprise also Kjellin syndrome, previously found to be associated with mutations in the SPG15 gene. We anticipate that degeneration of the central retina is a common and previously unrecognized feature in SPG11 related disease.

Repeatability in and interchangeability between the macular and the fast macular thickness map protocols: a study on normal eyes with Stratus optical coherence tomography.

PURPOSE: To collect a normal material and to compare the macular and the fast macular thickness map protocols regarding normal values and repeatability. METHODS: Sixty-seven individuals underwent three repeated scans with the macular thickness protocol; 45 of them also had three scans with the fast thickness protocol in Stratus optical coherence tomography (OCT). The maps were divided into nine ETDRS fields, where thickness values were presented. The repeatability was calculated as intraclass correlation coefficient (ICC), coefficient of variance (CV) and coefficient of repeatability (CR). For comparison between the two protocols, limits of agreement were determined according to Bland-Altman. RESULTS: Normal values for the two protocols were very close. Repeatability was high. ICC for all areas was 0.92-0.98. CV was less than 1% and CR was 6-8 µm for both protocols, with the exception of the fovea in the fast protocol (where CV was 1.44% and CR 12.4 µm). Limits of agreement between the two protocols were less than 10 µm as a rule. CONCLUSION: Normal values for the protocols are equal and they both have excellent repeatability. The fast macular map is a good alternative with the possible exception of the fovea, where variation is twice that of the macular thickness map.

A population-based study of macular thickness in full-term children assessed with Stratus OCT: normative data and repeatability.

PURPOSE: We aimed to determine normal macular thickness values, assessed with optical coherence tomography (OCT), in a population of full-term children of normal birthweight. METHODS: A total of 56 children, aged 5-16 years, randomly chosen from the population register, were examined with Stratus OCT. Only children with visual acuity < 0.2 logMAR, spherical equivalent of - 3 to + 3 D and astigmatism < 2 D were included. The fast macular map protocol was used and three examinations were performed in each eye. One eye was then randomized for further analyses. Mean values for the nine ETDRS areas, foveal minimum thickness and macular volume were calculated for 55 eyes. Coefficients of variance and intraclass correlations were calculated for each area. RESULTS: All children co-operated well and no child was excluded for lack of concentration. Mean ± standard deviation central macular thickness was 204 ± 19 µm. Mean total macular volume was 7.11 ± 0.35 mm(3). No correlations were found between age, gender and macular thickness. Coefficients of variance were < 2% and intraclass correlations were > 0.9 in all areas, except the foveal minimum. CONCLUSIONS: Normal values for macular thickness in healthy full-term children were reported. As the Stratus OCT provides normal values only for adults, these data are a better alternative for comparison with children with retinal abnormalities. We concluded that OCT is suitable for examining the retina in children aged 5-16 years and has the same high level of repeatability as in adults.

Early onset autosomal dominant spinocerebellar ataxia with miosis: four cases.

Previously, at least 29 different forms of autosomal dominant spinocerebellar ataxias (SCAs) have been described. We describe a family with four members through three generations with autosomal dominant ataxia in combination with miosis and hyperreflexia. This family's ataxia does not match any of the previously described SCAs and is probably a novel form of SCA. To continue with the search for the genetic background of this disease, more cases are needed.

Multifocal electroretinography and optical coherence tomography in two patients with solar retinopathy.

PURPOSE: Clinical investigation of central retinal dysfunction in two cases of solar retinopathy. METHODS: Two patients were examined for best corrected visual acuity (VA), fundus inspection, visual fields, multifocal electroretinography (mfERG) with a stimulus pattern of 241 hexagons and, at follow-up, also with optical coherence tomography (OCT). RESULTS: At the initial examination, mfERG revealed central retinal dysfunction, which had improved by the time of follow-up. In Case 1, a foveal oedema regressed over time, although VA remained slightly reduced. In Case 2, OCT showed spots of increased reflectivity corresponding to the patient's symptoms. CONCLUSION: Central retinal dysfunction due to solar retinopathy may improve over time. However, structural and functional changes may persist. This report illustrates that mfERG and OCT are useful tools for objective documentation of the pathology in solar retinopathy.

Optical coherence tomography in the diagnosis of juvenile X-linked retinoschisis.

PURPOSE: To describe the value of optical coherence tomography (OCT) as a diagnostic tool in the diagnosis of X-linked retinoschisis. METHODS: We report three boys aged between 8 and 17 years, diagnosed with X-linked retinoschisis. During investigations they were examined with OCT (Zeiss Humphrey OCT 1, upgraded version). Single scans of the central posterior pole and the region around the vascular arcades were obtained. Two of the boys underwent full-field ERG according to ISCEV standards. Genetic analysis was performed in all three boys, with sequencing of the XLRS gene. RESULTS: The OCT results revealed a pattern with a cleavage of the retina in two distinct planes, one deep (outer retina) and one superficial. This was very obvious in one patient and a similar but not as pronounced pattern was seen in the other two cases. The two layers were superficially connected with thin-walled, vertical palisades, separated by low reflective, cystoid spaces, confluent and most prominent in the foveal region. CONCLUSION: Full-field ERG and/or DNA analysis are well known methods used for diagnosis of X-linked juvenile retinoschisis. In this paper, we suggest that OCT can also be a helpful diagnostic tool.