Childhood-onset Leber hereditary optic neuropathy.

BACKGROUND: The onset of Leber hereditary optic neuropathy (LHON) is relatively rare in childhood. This study describes the clinical and molecular genetic features observed in this specific LHON subgroup. METHODS: Our retrospective study consisted of a UK paediatric LHON cohort of 27 patients and 69 additional cases identified from a systematic review of the literature. Patients were included if visual loss occurred at the age of 12 years or younger with a confirmed pathogenic mitochondrial DNA mutation: m.3460G>A, m.11778G>A or m.14484T>C. RESULTS: In the UK paediatric LHON cohort, three patterns of visual loss and progression were observed: (1) classical acute (17/27, 63%); (2) slowly progressive (4/27, 15%); and (3) insidious or subclinical (6/27, 22%). Diagnostic delays of 3-15 years occurred in children with an insidious mode of onset. Spontaneous visual recovery was more common in patients carrying the m.3460G>A and m.14484T>C mutations compared with the m.11778G>A mutation. Based a meta-analysis of 67 patients with available visual acuity data, 26 (39%) patients achieved a final best-corrected visual acuity (BCVA) ≥0.5 Snellen decimal in at least one eye, whereas 13 (19%) patients had a final BCVA <0.05 in their better seeing eye. CONCLUSIONS: Although childhood-onset LHON carries a relatively better visual prognosis, approximately 1 in 5 patients will remain within the visual acuity criteria for legal blindness in the UK. The clinical presentation can be insidious and LHON should be considered in the differential diagnosis when faced with a child with unexplained subnormal vision and optic disc pallor.

Keratometry obtained by corneal mapping versus the IOLMaster in the prediction of postoperative refraction in routine cataract surgery.

BACKGROUND: To establish whether simulated keratometry values obtained by corneal mapping (videokeratography) would provide a superior refractive outcome to those obtained by Zeiss IOLMaster (partial coherence interferometry) in routine cataract surgery. DESIGN: Prospective, non-randomized, single-surgeon study set at the The Royal United Hospital, Bath, UK, District General Hospital. PARTICIPANTS: Thirty-three patients undergoing routine cataract surgery in the absence of significant ocular comorbidity. METHODS: Conventional biometry was recorded using the Zeiss IOLMaster. Postoperative refraction was calculated using the SRK/T formula and the most appropriate power of lens implanted. Preoperative keratometry values were also obtained using Humphrey Instruments Atlas Version A6 corneal mapping. MAIN OUTCOME MEASURES: Achieved refraction was compared with predicted refraction for the two methods of keratometry after the A-constants were optimized to obtain a mean arithmetic error of zero dioptres for each device. RESULTS: The mean absolute prediction error was 0.39 dioptres (standard deviation 0.29) for IOLMaster and 0.48 dioptres (standard deviation 0.31) for corneal mapping (P = 0.0015). Keratometry readings between the devices were highly correlated by Spearman correlation (0.97). The Bland-Altman plot demonstrated close agreement between keratometers, with a bias of 0.0079 dioptres and 95% limits of agreement of -0.48-0.49 dioptres. CONCLUSIONS: The IOLMaster was superior to Humphrey Atlas A6 corneal mapping in the prediction of postoperative refraction. This difference could not have been predicted from the keratometry readings alone. When comparing biometry devices, close agreement between readings should not be considered a substitute for actual postoperative refraction data.

Optimization of biometry for intraocular lens implantation using the Zeiss IOLMaster.

PURPOSE: To compare the accuracy of biometry using conventional A-scan ultrasonography and partial coherence interferometry, and to improve the accuracy of biometry by sequential audit of postoperative refractive error. METHODS: The study was performed in three phases. In phase 1, 20 consecutive patients undergoing routine phacoemulsification underwent biometry using both A-scan ultrasonography and the Zeiss IOLMaster (ZIOLM). A single experienced optometrist refracted all patients 2 weeks after surgery. The errors between expected and achieved refraction were calculated and compared between the two methods. In phases 2 and 3, a further 22 and 20 patients, respectively, were recruited and only the ZIOLM was used for biometry. The manufacturer's suggested A-constant was refined and the error between expected and achieved refraction was calculated. RESULTS: In phase 1, the median unexpected error for the ZIOLM was +0.63 (interquartile range +0.368 to +1.015) and for A-scan biometry was - 0.24 (interquartile range - 1.335 to +0.802). In phase 1 65% of patients' postoperative refractions were found to be within 1.0 D of emmetropia using the ZIOLM (55% using A-scan biometry). Refinements to the A-constant improved this to 95% by phase 3. CONCLUSION: An error was identified in IOL power estimation with the ZIOLM, when using the manufacturer's recommended A-constant (recommended and previously optimized ultrasound A-constant 118.0; ZIOLM optimized A-constant 118.6). Serial modifications to the A-constant were successful in reducing the unexpected error to well within the tolerance limits of published international standards.

Optimization of biometry for intraocular lens implantation using the Zeiss IOLMaster.

PURPOSE: To compare the accuracy of biometry using conventional A-scan ultrasonography and partial coherence interferometry, and to improve the accuracy of biometry by sequential audit of postoperative refractive error. METHODS: The study was performed in three phases. In phase 1, 20 consecutive patients undergoing routine phacoemulsification underwent biometry using both A-scan ultrasonography and the Zeiss IOLMaster (ZIOLM). A single experienced optometrist refracted all patients 2 weeks after surgery. The errors between expected and achieved refraction were calculated and compared between the two methods. In phases 2 and 3, a further 22 and 20 patients, respectively, were recruited and only the ZIOLM was used for biometry. The manufacturer's suggested A-constant was refined and the error between expected and achieved refraction was calculated. RESULTS: In phase 1, the median unexpected error for the ZIOLM was+0.63 (interquartile range+0.368 to+1.015) and for A-scan biometry was --0.24 (interquartile range--1.335 to+0.802). In phase 1 65% of patients' postoperative refractions were found to be within 1.0 D of emmetropia using the ZIOLM (55% using A-scan biometry). Refinements to the A-constant improved this to 95% by phase 3. CONCLUSION: An error was identified in IOL power estimation with the ZIOLM, when using the manufacturer's recommended A-constant (recommended and previously optimized ultrasound A-constant 118.0; ZIOLM optimized A-constant 118.6). Serial modifications to the A-constant were successful in reducing the unexpected error to well within the tolerance limits of published international standards.

Human retinal molecular weight exclusion limit and estimate of species variation.

PURPOSE: To determine the maximum size of molecule capable of freely diffusing across human retina, referred to as the retinal exclusion limit (REL), and the location of any sites of high resistance to diffusion. To assess the degree of interspecies variation in the REL of three animals commonly used to model human disease. METHODS: Trephines of human neuroretina were mounted in a modified Ussing chamber. FITC-dextrans of various molecular weights (MWT) were dissolved in phosphate-buffered saline, and the rate of transretinal diffusion was determined over 24 hours with a spectrophotometer. The theoretical REL was calculated by extrapolating the linear relationship between the rate of diffusion and log(MWT). In separate experiments to determine the sites of barrier to diffusion, FITC-dextrans with a MWT greater than the calculated REL were applied to either the inner or outer retinal surface, processed as frozen sections, and viewed with a fluorescence microscope. Experiments to determine the REL were repeated in bovine, porcine, and rabbit retina. RESULTS: The REL in human tissue was 76.5+/-1.5 kDa (6.11+/-0.04 nm). The inner and outer plexiform layers formed the sites of highest resistance to diffusion. The REL in pigs, cattle, and rabbits were 60 +/- 11.5, 78.5 +/- 20.5, and 86 +/- 30 kDa, respectively (5.68 +/- 0.45, 6.18 +/- 0.61, and 6.38 +/- 0.88 nm). CONCLUSIONS: In humans, the inner and outer plexiform layers are sites of high resistance to the diffusion of large molecules, resulting in an REL of 76.5 kDa. There was only moderate interspecies variation in the REL of the animals studied, suggesting that they provide adequate models for the study of human transretinal macromolecular diffusion.