Genotype-phenotype associations in Danish patients with ocular and oculocutaneous albinism.

BACKGROUND: The study aimed to describe genotype-phenotype associations in patients with oculocutaneous and ocular-only albinism and to evaluate a set of diagnostic criteria proposed recently by Kruijt et al. MATERIALS AND METHODS: Genotype-phenotype associations in patients with a clinical diagnosis of albinism were studied based on imaging of hair and ocular features (nystagmus, iris color and translucency, fundus pigmentation and foveal development) and self-evaluated skin type. Patients were sub-grouped based on genetic findings. RESULTS: Patients with biallelic variants in TYR (n = 29), OCA2 (n = 22), other albinism genes (n = 13) or monoallelic variants in GPR143 (n = 13) were included as were 15 patients with a pure clinical diagnosis but no genetic findings. In descending order the most common findings were: foveal hypoplasia (any hypoplasia 95.2%, severe 88.0%), nystagmus (93.5%), iris translucency (any translucency 80.2%, moderate to severe 31.5%), misrouting on VEP (80.0%): fundus hypopigmentation (any hypopigmentation: 75.8%, severe 30.1%), fair skin type (73.8%), blue irides (62.0%), blonde hair (57.5%), and unpigmented eye lashes (39.1%). There were no phenotypic differences between the different genetic subgroups of albinism but patients with a pathogenic haplotype in TYR in combination with a classic variant had less iris translucency than patients with two classic variants in TYR. CONCLUSIONS: Ocular developmental features were the most common findings whereas phenotypic features related to pigmentation were less common findings but there were no genotype-phenotype correlations. All patients with a genetically confirmed diagnosis of albinism fulfilled the diagnostic criteria by Kruijt irrespective of genetic subtype.

Prefilled syringes for intravitreal injection reduce preparation time.

INTRODUCTION: The demand for intravitreal therapy has increased dramatically with the introduction of vascular endo-thelial growth factor inhibitors. Improved utilisation of existing resources is crucial to meeting the increased future demand. We investigated time spent preparing intravitreal injection treatment using either prefilled syringes or vials in routine clinical practice. METHODS: We video-recorded preparations of intravitreal injections (n = 172) for each preparation type (ranibizumab prefilled syringe (n = 56), ranibizumab vial (n = 56) and aflibercept vial (n = 60)) in a multi-centre time and motion study. The preparation times for each step were extracted from videos and the three preparation types were compared. RESULTS: Prefilled syringes eliminated several steps in the preparation process. Total preparation time was 40.3-45.1 sec. using vials, and the use of prefilled syringes saved 25.5 sec. (95% confidence interval (CI): 23.3-27.6 sec., p < 0.0001). The preparation time when aflibercept vials were used was 3.7 sec. (95% CI: 1.45-5.96 sec., p = 0.0014) longer than when ranibizumab vials were used. CONCLUSIONS: Prefilled syringes for intravitreal injections reduce preparation time by eliminating preparation steps that both entail a risk of contamination and are subject to variation. The amount of time saved may enable increased utilisation of existing resources and outsourcing to non-ophthalmologists. FUNDING: This study was supported by a grant from Novartis. The funders had no influence on the design of the study, analysis of the data, preparation of the manuscript or the decision to publish. TRIAL REGISTRATION: not relevant.

Axonal loss occurs early in dominant optic atrophy.

PURPOSE: This study set out to investigate retinal nerve fibre layer (RNFL) thickness and best corrected visual acuity (BCVA) in relation to age in healthy subjects and patients with OPA1 autosomal dominant optic atrophy (DOA). METHODS: We carried out a cross-sectional investigation of RNFL thickness and ganglion cell layer density in 30 healthy subjects and 10 patients with OPA1 DOA using optical coherence tomography (OCT). We then performed a regression analysis of RNFL thickness and BCVA versus age. RESULTS: Both healthy subjects and DOA patients demonstrated a gradual reduction in RNFL thickness with age; the relationship was best described statistically by a model that assumed a constant offset between the two groups. Best corrected VA decreased significantly with age in DOA patients, in whom BCVA was correlated with peripapillary RNFL thickness in the inferior and superior peripapillary quadrants and with total macular thickness at eccentricities of 500-3000 microm. The observations were best described by a constant offset of 41.9 microm separating the two groups and an annual decrease in RNFL thickness of 0.48 microm (p < 0.0001). In patients with DOA, increasing age was associated with decreasing BCVA (p = 0.046). CONCLUSIONS: This cross-sectional study found evidence of comparable age-related decreases in RNFL thickness in healthy subjects and in DOA patients, where the deficit in DOA patients is best described using a model that assumes the deficit between the groups does not vary with age. The gradual reduction of BCVA with age may be a consequence of a relative deficit in RNFL thickness that is established before the second decade of life.

Surveillance for retinopathy of prematurity in a Danish country. Epidemiological experience over 20 years.

PURPOSE: An updated analysis of the trends in a Danish county regarding retinopathy of prematurity (ROP), outlining its natural history over the years 1982-2001. METHODS: Epidemiological data are given of the 132 infants in the county with birth years 1998-2001 prospectively under surveillance for ROP. The customary national screening limits of gestational age (GA) and birthweight (BW) of 32 weeks/1750 g were generally adhered to. The findings are compared to five previous consecutive reports of a similar set-up, now making a total of 1123 who have been under surveillance. RESULTS: With focus on the 20 years' newborns at a higher risk for ROP in the county (GA/BW both under the above limits; n=591) the continuous improvement up to 1998--as reflected by ROP frequency, its severity, and risk levels according to GA/BW--appears to have been interrupted. Compared to the previous 4-year period, the percentage acquiring ROP in 1998-2001 increased from 10 to 31%, and four recent cases qualified for retinal ablation therapy, compared with zero in the previous 4-year period. However, there were no advanced stages (of at least ROP 3) in infants above 30 weeks/1500 g at delivery. CONCLUSIONS: (a) Using the ROP also as a neonatal treatment quality parameter, the present trend (progress stopped) should be followed attentively. So far, we have no clues regarding therapy-related or other causality. (b) Despite the suggested worsening, a lowering of the ophthalmic GA and BW screening limits now seems justifiable. With a view also to the high-risk Copenhagen data and the national childhood visual impairment register, a reduction of the values to 31 weeks/1500 g should be considered.

[Diabetic retinopathy in type 1 diabetics in the county of Frederiksborg]. / Diabetisk retinopati hos type 1-diabetikere i Frederiksborg Amt.

INTRODUCTION: Screening for diabetic retinopathy in a Danish county--are we following the recommendations? Incidence and risk factors of development and progression of diabetic retinopathy and prevalence of blindness among type 1 diabetics consulting the hospital of Hillerød are being described. MATERIAL AND METHODS: A total of 223 type 1 diabetics (debut < 30 years of age, insulin treated from first year of diagnosis) identified in a cross-sectional study in 1993 and followed until 2000 when data from last examination in the diabetes out-patient clinic and the ophthalmology clinic are registered. RESULTS: Ophthalmologists have screened nearly 97% of the patients as stated in the recommendations of the department. Only 2% were blind and only one patient went blind during the study period. The incidence of development of retinopathy was (54/119) 45%, (14/104) 13% had improved, (77/194) 40% had a progression of retinopathy, and (30/194) 15% had progressed to proliferative retinopathy. Risk factors found in the study match previously described risk factors. DISCUSSION: Audits encourage the implementation of screening programmes and hence reduce sight threatening diabetic retinopathy. The results of the study emphasize the importance of close co-operation between diabetes out-patient clinics and ophthalmologists and the necessity of regular screening. More audits are needed to bring screening for diabetic eye disease into focus and decrease the number of weak-sighted and blind diabetics.