Early ophthalmic growth deficits in preterm-born children are not compensated for during later development.

The renewed focus on eye growth in preterm-born children was primarily triggered by Danish cohort studies, including the Copenhagen Project, which focused on children born from 1959-1961. The retinotoxic effects of excessive oxygen on premature neonates had long been clarified and therapeutically adjusted for. Later, ultrasound oculometry and keratometry established that ocular size deficits, linked to development, also occurred in normally developing children, not just frail outliers. This indicated that general catch-up had not been achieved. This paper discusses whether one early segment of eye development does not occur in preterm, and here even in more robust neonates, without later compensation.

Scleroderma en Coup de Sabre, Parry-Romberg Hemifacial Atrophy and Associated Manifestations of the Eye, the Oral Cavity and the Teeth: A Danish Follow-Up Study of 35 Patients Diagnosed between 1975 and 2015.

BACKGROUND: Scleroderma en coup de sabre (ECDS) and Parry-Romberg idiopathic hemifacial atrophy (IHA) may affect the eyes, oral cavity, teeth and possibly the brain. OBJECTIVE: Systematic follow-up study of ECDS/IHA-associated manifestations including ophthalmic and dental status. METHODS: Medical records of ECDS and IHA patients diagnosed in a 40-year period (1975-2015) were reviewed, and patients were re-examined. RESULTS: Thirty-five patients were included. Twenty-two patients (63%) had ECDS and 4 patients (11%) IHA. In 9 cases (26%), ECDS and IHA were found in the same patient. The ipsilateral eye was affected in 9 patients (26%). Ipsilateral abnormalities of the teeth and the tongue were found in 13 (46%) out of 28 examined. Eleven (31%) had extrafacial scleroderma on the trunk or the extremities. Neurological findings were not verified as ECDS/IHA related. CONCLUSION: ECDS and IHA are related and often overlap with concomitant affections of the connective tissues of the face on the ipsilateral side. Ocular and dental abnormalities are common and follow the distribution of the primary affection, for example, a paramedian line in the front and segmental affection of the maxilla and the mandible. The affections point to predisposing dysmorphogenetic events in embryonal life affecting the face, with abnormality of crest cells at the stage when they migrate from behind over the scalp or laterally to the face to mix up with mesenchymal tissues of the frontonasal, maxillary and mandibular processes. The study emphasizes that routine evaluation of ECDS and IHA should include ophthalmological and dental specialist examinations.

The Longitudinal Danish High Myopia Study, Cohort 1948: at age 66 years visual ability is only occasionally affected by visual field defects.

PURPOSE: A descriptive study on visual fields, as part of a 50-year follow-up of high myopia in an unselected cohort-based Danish sample, now aged 66 years. METHODS: In a Copenhagen 1948 birth cohort (n = 9243), 39 individuals aged 14 years were identified with myopia of at least -6 D, and with regular clinical follow-ups since then. In 2002 (n = 34, age 54 years) and 2008 (n = 32, age 60), the individual ambulatory visual field was outlined by kinetic Goldmann large object perimetry (IV or V,4e). At age 66 years, 28 attended for the 2014-2015 follow-up, at which smaller Goldmann objects (II and I,4e) were added, further to identify relative defects. RESULTS: Repeated large object perimetry disclosed statistically significant general peripheral narrowing over the 12-13-year test period, though slight and without practical implications. Two new cases showing absolute defects were however added to the three already known. The addition of small Goldmann objects disclosed relative defects in another eight participants, in some to suggest a refraction-related pattern (fundus ectasia; uncorrected high myopia). However, comparing eyes with and without defects, statistical importance could not be attached to the degree of myopia, fundus ectasia or optic disc morphology (χ2 , n.s.). CONCLUSION: (i) Serial large object Goldmann isopters over the 'senior' decade up to age 66 demonstrated a slight general peripheral narrowing by age of visual fields in high myopia. (ii) Overall 42% of the participants had absolute or relative defects (in 5 and 8, respectively), however, without socio-visual consequences when binocular. (iii) Visual field loss by age still appears a minor issue in clinically unselected high myopia.

Ophthalmic findings in linear scleroderma manifesting as facial en coup de sabre.

BACKGROUND: To evaluate ophthalmic involvement in a long-term series of patients with en coup de sabre (ECS) close to the eye based on the hypothesis that this is not commonly affected, or simply under-reported. METHODS: An observational study of ophthalmological findings in patients from Copenhagen University Dermatology Clinics. A standard eye examination further included exophthalmometry, axial length and keratometry (IOLMaster), and horizontal eye muscle thickness (B-scan ultrasonography). RESULTS: Thirty-one consecutive patients were included from 2014 to 2015 (25 females, 6 males; median age, 33 years; range, 11-71 years). Twenty-seven patients had undergone ophthalmic evaluation more than once (observation time, 1-31 years; median, 7 years). Most eyes were normal or had currently adapted to eventual adnexal lesions and to insidious changes in eye position and/or motility. However, significant ipsilateral complications had developed related to 8 eyes, where two patients had more than one disorder. The ophthalmic pathologies were: blind eye (n = 2) due to adult age keratopathy/perforation and to Coats-like retinal detachment in childhood; restricted eye motility and diplopia (n = 2); acquired corneal astigmatism (n = 2); and dense cataract with light sense only (n = 1). Two patients had optic neuritis-like presentations, and lacrimal sac pathology occurred in one. CONCLUSIONS: The main ophthalmic focus possibly explained the high proportion of significant lesions in this patient series (in 8 of 31). In addition to the established feature of enophthalmos, the oculometric evidence suggested smaller eye and rectus muscle involvement, interpreted as a secondary (late) negative trophic effect of the overlying skin disorder on eye structures.

Choroidal thickness at age 66 years in the Danish high myopia study cohort 1948 compared with follow-up data on visual acuity over 40 years: a clinical update adding spectral domain optical coherence tomography.

BACKGROUND AND PURPOSE: A population-based Copenhagen birth year 1948 cohort with high myopia recorded since age 14 years (spherical equivalent less than or equivalent to -6 D) has been followed over 50 years. Despite complications, current follow-ups have outlined a better visual prognosis than usually drawn from selected clinical series in the literature. For the present status at age 66 years, focus was on visual ability and choroidal thickness. METHODS: Twenty-eight of the original 39 participants were available in 2014. Medical history was updated. Best-corrected visual acuity (BCVA) data were compared with subfoveal choroidal thickness (SFCT), now measured by enhanced depth optical coherence tomography. RESULTS: Due to at least better eye visual acuity (VA), all patients had maintained their everyday visual capacity. Only one participant was marginal regarding visual status for a driver's licence; low vision was not on record. Based on all eyes, choroidal thickness correlated negatively with axial length (AL), which also held for the fraction with high myopia (AL >26.5 mm). In high myopia, the mean choroidal subfoveal thickness was 114 ± 75 µm versus 182 ± 94 µm in lower myopia (p = 0.01). CONCLUSION: Despite the generally maintained individual visual capacity in the series, significant correlation could be demonstrated between SFCT and (i) axial elongation and (ii) recorded VA, with a negative and a positive sign, respectively. Overall, the visual prognosis was relatively benign, in particular when compared with the selected high myopia hospital series that predominate in the ophthalmic literature.

Early postnatal hyperglycaemia is a risk factor for treatment-demanding retinopathy of prematurity.

BACKGROUND: To investigate whether neonatal hyperglycaemia in the first postnatal week is associated with treatment-demanding retinopathy of prematurity (ROP). METHODS: This is a Danish national, retrospective, case-control study of premature infants (birth period 2003-2006). Three national registers were searched, and data were linked through a unique civil registration number. The study sample consisted of 106 cases each matched with two comparison infants. Matching criteria were gestational age (GA) at birth, ROP not registered and born at the same neonatal intensive care unit. Potential 'new' risk factors were analysed in a multivariate logistic regression model, while adjusted for previously recognised risk factors (ie, GA at birth, small for gestational age, multiple birth and male sex). RESULTS: Hospital records of 310 preterm infants (106 treated; 204 comparison infants) were available. Nutrition in terms of energy (kcal/kg/week) and protein (g/kg/week) given to the preterm infants during the first postnatal week were statistically insignificant between the study groups (Mann-Whitney U test; p=0.165/p=0.163). Early postnatal weight gain between the two study groups was borderline significant (t-test; p=0.047). Hyperglycaemic events (indexed value) were statistically significantly different between the two study groups (Mann-Whitney U test; p<0.001). Hyperglycaemia was a statistically independent risk factor (OR: 1.022; 95% CI 1.002 to 1.042; p=0.031). CONCLUSION: An independent association was found between the occurrence of hyperglycaemic events during the first postnatal week and later development of treatment-demanding ROP, when adjusted for known risk factors.

Ultrasonic mirror image from ruthenium plaque facilitates calculation of uveal melanoma treatment dose.

BACKGROUND/AIMS: To present a new method to determine dose depth and the distance from the concave side of the plaque to the tumour base in patients with uveal melanoma treated with ruthenium-106 based on ultrasonic mirror image. METHODS: We used the mirror image associated with ultrasound during plaque brachytherapy to determine intraobserver reproducibility and interobserver agreement between two surgeons. 230 eyes with primary uveal melanoma were included in a retrospective analysis to determine the distance from the plaque to the tumour base using ultrasound. A phantom study was used to illustrate the effects on radiation dose to apex of the tumour when the dose depth was incorrectly determined. Doses to apex of the tumour were determined using Plaque Simulator. RESULTS: The intraobserver variation in dose depth measurement with plaque was significantly lower than for measures without plaque (p<0.001). Agreement between the surgeons was better with a plaque in place. Distances from the plaque to the tumour base were distributed with mean=0.99 (median: 1, range: 0.1-2.9 mm). From the phantom study, it was clear that the tumour did not receive the prescribed 100 Gy if the dose depth was incorrectly determined. CONCLUSIONS: The dose depth in patients with uveal melanoma must be measured accurately for correct calculation of the radiation dose to the apex of the tumour. Repeated in vivo and in vitro ultrasound measurements of dose depth showed higher variance than measurements using the mirror image produced from a ruthenium plaque. Using the mirror image thus help to improve the dose calculation.

Optic disc drusen: longitudinal aspects, with emphasis on visual field constriction and enlarged blind spot: a retrospective hospital-based clinical series.

PURPOSE: To examine long-term data on optic disc drusen (ODD) from an outpatient hospital series that indicated more cases with advanced visual field constriction than is apparent from other clinical reports. The underlying pathophysiology is discussed, also with regard to enlarged blind spot, which, in view of the small disc at risk, may seem a paradox. METHODS: This is an observational retrospective study on an eye clinic series (n = 49), focusing on visual acuity, kinetic/static perimetry, and longitudinal trends, to include the question of eventual visual incapacity. RESULTS: Forty-nine patients (32 female and 17 male; bilateral ODD in 45) aged 5-76 years (median age 29 years for both sexes) were included in the study. Observation time was 1-54 years, with serial data recorded over at least 3 years in 25 patients. Visual field defects were found in 32 patients, with ODD considered responsible for the visual field defects demonstrated. Advanced unilateral concentric constriction (for the largest Goldmann object) was recorded in 10 patients, and bilaterally in 2. With regard to nonexplanatory side diagnoses, 2 patients had pituitary adenoma, 1 had a cavernous sinus meningioma, and 1 had neurosurgery for an arachnoid cyst. CONCLUSIONS: We found more cases of marked visual field constriction than reported in other clinical series. A few such cases appeared acute and vascular, but the main trend was clinically quiet over time. All 49 patients could manage visually in daily life.

Neonatal Risk Factors for Treatment-Demanding Retinopathy of Prematurity: A Danish National Study.

PURPOSE: One goal of the study was to identify "new" statistically independent risk factors for treatment-demanding retinopathy of prematurity (ROP). Another goal was to evaluate whether any new risk factors could explain the increase in the incidence of treatment-demanding ROP over time in Denmark. DESIGN: A retrospective, register-based cohort study. PARTICIPANTS: The study included premature infants (n = 6490) born in Denmark from 1997 to 2008. METHODS: The study sample and the 31 candidate risk factors were identified in 3 national registers. Data were linked through a unique civil registration number. Each of the 31 candidate risk factors were evaluated in univariate analyses, while adjusted for known risk factors (i.e., gestational age [GA] at delivery, small for gestational age [SGA], multiple births, and male sex). Significant outcomes were analyzed thereafter in a backward selection multiple logistic regression model. MAIN OUTCOME MEASURES: Treatment-demanding ROP and its associations to candidate risk factors. RESULTS: Mechanical ventilation (odds ratio [OR], 2.84; 95% confidence interval [CI], 1.99-4.08; P < 0.01) and blood transfusion (OR, 1.97; 95% CI, 1.20-3.14; P = 0.01) were the only new statistically independent risk factors, in addition to GA at delivery, SGA, multiple births, and male sex. Modification in these prognostic factors for ROP did not cause an increase in treatment-demanding ROP. CONCLUSIONS: In a large study population, blood transfusion and mechanical ventilation were the only new statistically independent risk factors to predict the development of treatment-demanding ROP. Modification in the neonatal treatment with mechanical ventilation or blood transfusion did not cause the observed increase in the incidence of preterm infants with treatment-demanding ROP during a recent birth period (2003-2008).

Refraction and visual acuity in a national Danish cohort of 4-year-old children of extremely preterm delivery.

PURPOSE: A recent threefold increase in laser treatment for advanced retinopathy of prematurity (ROP) triggered a nationwide preschool ophthalmic and developmental status among extremely preterm survivors. Here, we discuss refraction and visual acuity. METHODS: Survivors (n = 178) from a national birth cohort (February 2004 to March 2006) of gestational age <28 weeks (PT) and 56 full-term (FT) controls attended for evaluation at age 4 years. Cycloplegic refraction and keratometry were achieved by Retinomax autokeratorefractor and visual acuities by symbol recognition (HOTV, logMAR). RESULTS: The refractive distribution presented a myopic tail (4.5%) and a hyperopic tail (11.9% ≥+2.5 D) as special preterm features, and corneas were more curved. Astigmatism and anisometropia were only marginally increased, and visual acuities were generally good. Best-corrected binocular median logMAR visual acuity was 0.1 in FT and 0.2 in PT, in Snellen equivalents 0.8 and 0.63. Snellen acuity ≤0.5 occurred across the ROP subgroups, but mainly in those with at least ROP stage 3. Two children had low vision. CONCLUSIONS: The overall fair outcome for refraction and function is in accordance with other recent northern Europe experience. The results differ in particular from the poorer ophthalmic outcomes reported in the pioneer US treatment studies (cryotherapy for ROP and ETROP). The diode laser ablations (n = 32) appeared effective in our series; except one child, all treated subjects had good or fair social vision at the age of 4 years.

Ophthalmic experience over 10 years in an observational nationwide Danish cohort of Fabry patients with access to enzyme replacement.

PURPOSE: Enzyme replacement therapy (ERT) was offered from year 2001 to patients with Fabry disease. The ophthalmic experience was analysed, as part of a general 10-year status. METHODS: A retrospective observational series comprising 39 patients (25 females, 14 males) closely followed by the endocrinologists, and with regular ophthalmic control. Time of inclusion was when the option of ERT was started, at age 11-60 years. Eye data (standard eye examination, including retinal imaging) were incomplete in five, due to death or non-attendance, and five patients had refused treatment. RESULTS: Vision was normal throughout, except in two young males with total unilateral central retinal artery occlusion, prior to and during enzyme replacement, respectively. Cornea verticillata and conjunctival vessel ectasies were common. Tortuosity of retinal arterioles and venules was recorded in eight and 18 patients, respectively, and phlebopathy in 22, although generally without evidence of loss of vessel wall integrity. Systemic vascular lesions with or without loss of function were recorded for kidney (n = 23), heart (n = 17) and brain (n = 7), and an association was suggested between nephropathy and abnormal morphology of retinal vessels. CONCLUSIONS: Thirteen of 32 patients on ERT showed a reduction of corneal deposits over the study period. Abnormal ocular vessel morphology was a frequent finding. In contrast to the function loss related to systemic ischaemic lesions, we found no indication of impairment of visual parameters in 37. Compared to other Fabry series, two of 39 patients with serious unilateral occlusive retinal disease may appear a high number. The presence of retinal tortuosity is discussed, possibly reflecting haemodynamic events related to vessel wall deposits, but could also be 'constitutional', as part of the Fabry inheritance.

Human parallels to experimental myopia? A literature review on visual deprivation.

Raviola and Wiesel's monkey eyelid suture studies of the 1970s laid the cornerstone for the experimental myopia science undertaken since then. The aim has been to clarify the basic humoral and neuronal mechanisms behind induced myopization, its eye tissue transmitters in particular. Besides acquiring new and basic knowledge, the practical object of the research is to reduce the burden of human myopia around the world. Acquisition and cost of optical correction is one issue, but associated morbidity counts more, with its global load of myopia-associated visual loss and blindness. The object of the present PubMed literature-based review is to evaluate apparent similarities between experience from disturbed imaging in experimental laboratory science and varieties within the spectrum of childhood human myopia. So far, the main impression is that macroscopical optical deprivation appears absent in the prevalent types of human myopia, nor is myopia a regular sequel where early eye pathology has led to poor imaging and optical deprivation. Optical aberrations of a higher order are a relatively new issue in myopia research, and microstructural deprivation is only marginally dealt within the survey. Links between experimental and human myopia appear mainly occasional, and with only few examples in humans where factual parallels appear credible. Clinical and epidemiological data on refraction remain important, in particular with a view to life style and environmental factors. Such knowledge may further serve as inspiration to the laboratory research, which aims at solving the basic enigmas on a tissue level.

Juvenile eye growth, when completed? An evaluation based on IOL-Master axial length data, cross-sectional and longitudinal.

PURPOSE: To test Sorsby's classical statement of axial eye growth as completed at the age of 13 years, with a view also to differentiating between basic eye growth and juvenile elongation associated with eventual refractive change towards myopia. METHODS: (i) A total of 160 healthy eyes close to emmetropia were included in a cross-sectional set-up (age 4-20 years, 91 males, 69 females), and (ii) 78 longitudinal data sets (67 male and 11 female annual repeat exams over 2-7 years, n=30; age span 4-19 years) were available for evaluating individual axial elongation. The IOL-Master equipment was preferred for conventional ultrasound oculometry due to its extreme repeatability of measuring values, thus making it well fitted for evaluating very small differences. In particular, this had bearing for the decelerating end phase of growth in the longitudinal investigation. RESULTS: Sorby's statement about age 13 as general limit found support from the cross-sectional data, which suggested stable emmetropic eye size from about 11-12 years, with an average apparently outgrown male emmetropic value of 23.5 mm versus females' 22.9 mm. The longitudinal data, however, showed emmetropic growth also beyond this age, with individual data to establish continued axial elongation also at age 13-18 years. The final basic teenage growth is however minute and without practical implications. CONCLUSIONS: Individual ocular growth curves have indicated axial elongation to occur also after the age of 13 years. With regard to the - mainly academic - discrepancy between cross-sectional and longitudinal results, bigger samples are needed, and the juvenile myopic trend has to be acknowledged.

Infantile nystagmus and visual deprivation: foveal instability and refractive development in a low vision register series.

PURPOSE: To evaluate whether effects of early foveal motor instability due to infantile nystagmus might compare to those of experimental visual deprivation on refraction in a childhood series. METHODS: This was a retrospective analysis of data from the Danish Register for Blind and Weaksighted Children with infantile nystagmus recorded as prime diagnosis. We perused 90 records of children now aged 10-17 years, some of whom eventually exceeded the register borderline of 0.3 as best-corrected visual acuity. Spherical equivalent refraction was the primary outcome parameter, but visual acuity, astigmatism, and age were further considered. The series comprised 48 children with nystagmus as single diagnosis, whereas 42 had clinical colabels (Down syndrome [13], dysmaturity [9], and mental retardation, encephalopathy [20]). RESULTS: Median binocular visual acuity was 0.3 in the full series, and median refraction was emmetropia in all subgroups. Compared with Danish control data, myopia was over-represented, and generally of juvenile onset. The Down syndrome subgroup was separated from the remainder by an even higher myopia prevalence. Astigmatism above 1 D cylinder value was recorded in 52% of all cases. CONCLUSIONS: The prevalence of myopia and astigmatism was higher among children with nystagmus than in controls. Myopia was mainly juvenile, and not related to the period of infancy when the motor foveal smear is considered most disturbing and possibly influencing visual development.

Bilateral optic neuropathy in a patient with familial amyloidotic polyneuropathy.

Amyloidogenic transthyretin (ATTR)-related familial amyloidotic polyneuropathy (FAP) is an autosomal-dominant hereditary disease characterised by slowly progressive peripheral sensorimotor and autonomic neuropathy and tissue involvement of the heart, kidneys and central nervous system. Secondary glaucoma has been reported following intraocular surgery, but optic nerve involvement unrelated to glaucoma has not previously been described. We reported a male patient in his late 40s when deceased, who previously had a liver transplant in order to reduce the abnormal protein synthesis underlying his FAP ATTR Val30Met mutation. After 11 years of ophthalmic follow-up best-corrected visual acuity was 20/100 in his seeing eye, which further had visual field findings suggestive of optic neuropathy. This was also the diagnosis underlying the preceding insidious full loss of vision in the fellow eye, with colour Doppler imaging to support an ischaemic aetiology. To our knowledge, this is the first report of ischaemic optic neuropathy in this familial amyloid disorder.

Eye features in three Danish patients with multisystemic smooth muscle dysfunction syndrome.

BACKGROUND: A de novo mutation of the ACTA2 gene encoding the smooth muscle cell α-actin has been established in patients with multisystemic smooth muscle dysfunction syndrome associated with patent ductus arteriosus and mydriasis present at birth. OBJECTIVE: To describe the structural ocular findings in three Danish children with this new syndrome and evaluate the possible functional consequences for visual development of the poorer imaging condition. RESULTS: Unresponsive mydriatic pupils with scalloping wisps of persistent pupillary membrane from the iris collarette were an early indicator of this rare genetic disorder in all three cases. Tortuousity of retinal arterioles was the main posterior pole finding, apparent during the first year of life and with a tendency to increase with age. In one case, it progressed to an aneurysmal-like state with breakdown of the blood-retinal barrier. CONCLUSIONS: Congenital mydriasis is an extremely rare pupil anomaly and is the feature for the early diagnosis of this new syndrome. The ophthalmologist should act in close collaboration with other specialists owing to the risk of aortic and cerebrovascular diseases and other complications associated with this disorder.

Cerebral damage may be the primary risk factor for visual impairment in preschool children born extremely premature.

OBJECTIVES To investigate the importance of cerebral damage and retinopathy of prematurity (ROP) for visual impairment in preschool children born extremely premature and to determine the primary risk factor of the two. METHODS A clinical follow-up study of a Danish national cohort of children born extremely premature (gestational age, <28 weeks). The study sample consisted of 262 extremely preterm children born between February 13, 2004, and March 23, 2006, of whom 178 children (67.9%) participated. A matched control group consisted of 56 term-born children (gestational age, 37 to <42 weeks). All participants were identified through the National Birth Register and invited to participate in a clinical examination. The children were evaluated with regard to visual acuity, foveal sequelae, and maximum ROP stage and the presence of global developmental deficits (an indicator for cerebral damage) that was measured by the Ages and Stages Questionnaire. RESULTS Global developmental deficits and foveal sequelae occurred more often in extremely preterm children than in term-born control children and increased with ROP severity (χ2 test; P = .11 and P < .001, respectively). Global developmental deficits, moderate to severe foveal abnormality, and ROP treatment were independently associated with visual impairment (P < .05, for better and worse eyes). A stepwise multiple logistic regression for better-eye logarithmic visual acuities of 0.3 or greater (Snellen scale, ≤0.5) yielded an odds ratio of 8.7 (95% CI, 3.0-25.2; P < .001) for global developmental deficit and 6.3 (95% CI, 2.2-18.5; P < .001) for moderate to severe foveal sequelae. CONCLUSION Cerebral damage and ROP are independent risk factors for visual impairment in children born extremely premature, and cerebral damage may be the primary risk factor.