Measurement of ocular aberrations in downward gaze using a modified clinical aberrometer

Changes in corneal optics have been measured after downward gaze. However, ocular aberrations during downward gaze have not been previously measured. A commercial Shack-Hartmann aberrometer (COAS-HD) was modified by adding a relay lens system and a rotatable beam splitter to allow on-axis aberration measurements in primary gaze and downward gaze with binocular fixation. Measurements with the modified aberrometer (COAS-HD relay system) in primary and downward gaze were validated against a conventional aberrometer. In human eyes, there were significant changes (p<0.05) in defocus C(2,0), primary astigmatism C(2,2) and vertical coma C(3,−1) in downward gaze (25 degrees) compared to primary gaze, indicating the potential influence of biomechanical forces on the optics of the eye in downward gaze. To demonstrate a further clinical application of this modified aberrometer, we measured ocular aberrations when wearing a progressive addition lens (PAL) in primary gaze (0 degree), 15 degrees downward gaze and 25 degrees downward gaze

LONGITUDINAL STUDY OF RPE65-ASSOCIATED INHERITED RETINAL DEGENERATIONS

PURPOSE: To study the disease course of RPE65-associated inherited retinal degenerations (IRDs) as a function of the genotype, define a critical age for blindness, and identify potential modifiers. METHODS: Forty-five patients with IRD from 33 families with biallelic RPE65 mutations, 28 stemming from a genetic isolate. We collected retrospective data from medical charts. Coexisting variants in 108 IRD-associated genes were identified with Molecular Inversion Probe analysis. RESULTS: Most patients were diagnosed within the first years of life. Daytime visual function ranged from near-normal to blindness in the first four decades and met WHO criteria for blindness for visual acuity and visual field in the fifth decade. p.(Thr368His) was the most common variant (54%). Intrafamilial variability and interfamilial variability in disease severity and progression were observed. Molecular Inversion Probe analysis confirmed all RPE65 variants and identified one additional variant in LRAT and one in EYS in two separate patients. CONCLUSION: All patients with RPE65-associated IRDs developed symptoms within the first year of life. Visual function in childhood and adolescence varied but deteriorated inevitably toward blindness after age 40. In this study, genotype was not predictive of clinical course. The variance in severity of disease could not be explained by double hits in other IRD genes

LONGITUDINAL STUDY OFRPE65-ASSOCIATED INHERITED RETINAL DEGENERATIONS

Purpose: To study the disease course ofRPE65-associated inherited retinal degenerations (IRDs) as a function of the genotype, define a critical age for blindness, and identify potential modifiers. Methods: Forty-five patients with IRD from 33 families with biallelicRPE65mutations, 28 stemming from a genetic isolate. We collected retrospective data from medical charts. Coexisting variants in 108 IRD-associated genes were identified with Molecular Inversion Probe analysis. Results: Most patients were diagnosed within the first years of life. Daytime visual function ranged from near-normal to blindness in the first four decades and met WHO criteria for blindness for visual acuity and visual field in the fifth decade. p.(Thr368His) was the most common variant (54%). Intrafamilial variability and interfamilial variability in disease severity and progression were observed. Molecular Inversion Probe analysis confirmed allRPE65variants and identified one additional variant inLRATand one inEYSin two separate patients. Conclusion: All patients withRPE65-associated IRDs developed symptoms within the first year of life. Visual function in childhood and adolescence varied but deteriorated inevitably toward blindness after age 40. In this study, genotype was not predictive of clinical course. The variance in severity of disease could not be explained by double hits in other IRD genes

Optical coherence tomography and scanning laser polarimetry in normal, ocular hypertensive, and glaucomatous eyes

PURPOSE: To evaluate the relationship between visual function and retinal nerve fiber layer measurements obtained with scanning laser polarimetry and optical coherence tomography in a masked, prospective trial. METHODS: Consecutive normal, ocular hypertensive, and glaucomatous subjects who met inclusion and exclusion criteria were evaluated. Complete ophthalmologic examination, disk photography, scanning laser polarimetry, optical coherence tomography, and automated achromatic perimetry were performed. RESULTS: Seventy-eight eyes of 78 patients (17 normal, 23 ocular hypertensive, and 38 glaucomatous) were enrolled (mean age, 56.8 ± 11.5 years; range, 26 to 75 years). Eyes with glaucoma had significantly greater neural network scores on scanning laser polarimetry and lower maximum modulation, ellipse modulation, and mean retinal nerve fiber layer thickness measured with optical coherence tomography compared with normal and ocular hypertensive eyes, respectively (all P < .005). Significant associations were observed between neural network number ( r = −.51, r = .03), maximum modulation ( r = .39, r = −.32), ellipse modulation ( r = .36, r = −.28), and optical coherence tomography–generated retinal nerve fiber layer thickness ( r = .68, r = −.59) and visual field mean deviation and corrected pattern standard deviation, respectively. All scanning laser polarimetry parameters were significantly associated with optical coherence tomography–generated retinal nerve fiber layer thickness. CONCLUSION: Optical coherence tomography and scanning laser polarimetry were capable of differentiating glaucomatous from nonglaucomatous populations in this cohort; however considerable measurement overlap was observed among normal, ocular hypertensive, and glaucomatous eyes. Retinal nerve fiber layer structural measurements demonstrated good correlation with visual function, and retinal nerve fiber layer thickness by optical coherence tomography correlated with retardation measurements by scanning laser polarimetry

Ectopia lentis et pupillae in four generations caused by novel mutations in the ADAMTSL4 gene

Item does not contain fulltextOBJECTIVES: To identify the phenotype, genetic defect and inheritance pattern of ectopia lentis et pupillae (ELP) in a large Dutch family, previously diagnosed as presumed autosomal dominant ELP because of the occurrence of ELP in three generations. DESIGN: A clinical and genetic study of children and adults. PARTICIPANTS: Eight patients of the ELP family, including five new patients from the youngest generation. METHODS: Standard ophthalmological examinations were performed. For molecular genetic analysis, the coding region of ADAMTSL4 was sequenced. Main outcome measures were the ocular phenotype of the new ELP patients, the inheritance pattern and the identification of mutations in the ADAMTSL4 gene in the family. RESULTS: Of the eight patients with ectopia lentis, seven fulfilled the clinical diagnostic criteria of ELP. Molecular genetic analysis of these seven patients disclosed two novel mutations in the ADAMTSL4 gene: homozygous (p.Q752X/p.Q752X) in six patients and compound heterozygous (p.Q752X/p.Q758fs) in one patient. Heterozygosity in phenotypically normal parents proved autosomal recessive (AR) inheritance. The pseudodominant inheritance pattern can be explained by high carrier frequency in this small community and/or consanguinity. CONCLUSIONS: Patients from a family with ELP in four generations have AR ELP caused by novel mutations in ADAMTSL4. The clinical presentation of ELP can be variable, but all patients of our study with homozygous p.Q752X mutation have ectopia lentis and pupillary dysfunction in common