Peter A. Quiros

Extensive investigation of a large Brazilian pedigree of 11778/haplogroup J Leber hereditary optic neuropathy

PURPOSE To conduct systematic epidemiologic, neuro-ophthalmologic, psychophysical, and mitochondrial DNA (mtDNA) genetic examinations on a newly identified pedigree with Leber hereditary optic neuropathy (LHON). DESIGN Observational population cohort study. METHODS A prospective investigation of an entire Brazilian LHON family. SETTING A field investigation by an international team conducted in a remote part of Brazil. STUDY POPULATION We evaluated 265 (both eyes) of the 328 living family members of this LHON pedigree. Only members of this pedigree were studied. Those entering the pedigree as spouses were used as controls. OBSERVATION PROCEDURES We conducted epidemiologic interviews emphasizing possible environmental risk factors, comprehensive neuro-ophthalmologic examinations, psychophysical tests, Humphrey visual field studies, fundus photography, and blood testing for mitochondrial genetic analysis. RESULTS We reconstructed a seven-generation maternal lineage descended from a common ancestor dating to the 1870s. All maternally related family members were invariably homoplasmic 11778 with a haplogroup J mtDNA, 33 being affected, of which 22 are still living. With each subsequent generation, there was a progressive decrease of penetrance, and only males were affected in the last two generations. A significant exposure (greater than 95% confidence intervals) to a variety of environmental risk factors characterized the affected individuals, with smoking as the most common (P <.01). Both affected and carriers (95% confidence intervals) presented with a significantly lower incidence of hypertension and high cholesterol compared with the control group (P <.05). CONCLUSIONS Almost 95% of a 328-living-member pedigree with LHON 11778/J haplogroup was comprehensively studied. Our initial results indicate the strong influence of environmental risk factors. The remarkably reduced incidence of cardiovascular risk in the maternal lineage is discussed. Further genetic analysis may reveal a role for the nuclear genome.

Corneal sensation after laser in situ keratomileusis.

PURPOSE To report the time course for the return of corneal sensation following laser in situ keratomileusis (LASIK). SETTING University-based retractive surgery practice. METHODS Twenty-eight eyes of 18 patients having LASIK were evaluated. Preoperative and postoperative corneal sensation at the nasal flap hinge, at the central cornea, and within the temporal flap edge were measured before and after LASIK for a 3 week period using the Cochet-Bonnet esthesiometer (Luneau). RESULTS Corneal sensation initially decreased in all 3 positions of the flap measured after LASIK; the greatest decrease was in the central cornea. Near preoperative corneal sensation returned by 3 weeks. The degree of sensation loss did not appear to correlate with the ablation depth. CONCLUSION Corneal sensation is significantly decreased for approximately 2 to 3 weeks after LASIK, centrally greater than nasally at the flap hinge or temporally within the flap edge, but it generally returns to near the preoperative level by 3 weeks postoperatively.

Colour vision defects in asymptomatic carriers of the Leber's hereditary optic neuropathy (LHON) mtDNA 11778 mutation from a large Brazilian LHON pedigree: a case‐control study

Aims: To determine if asymptomatic carriers from a previously identified large pedigree of the Leber’s hereditary optic neuropathy (LHON) 11778 mtDNA mutation have colour vision deficits. Methods: As part of a comprehensive analysis of over 200 members of a large Brazilian LHON pedigree spanning seven generations, colour vision tests were obtained from 91 members. Colour vision was tested one eye at a time using the Farnsworth-Munsell 100 (FM-100) hue colour vision test. The test was administered under uniform conditions, taking into account: ambient light levels, daylight colour temperature of 6700 kelvin, and neutral uniform background. Tests were scored using the FM-100 MS-Excel computer scoring program. Defects were determined and categorised as tritan, deutan, or protan. Categorisation of each dyschromatopsia was based on review of demonstrated axis computer generated plots and age adjusted error scores which coincided with Verriest 95% confidence intervals. Only the axis with the greatest magnitude error score was used to classify the defect. 55 of the 91 test subjects were LHON mtDNA 11778 J haplotype mutation carriers, proved by mtDNA analysis. The remaining 36 subjects were age matched non-blood relatives (off pedigree), who served as controls. Results: 27 of 55 carriers (49.10%) were shown to have colour vision defects in one or both eyes. 13 of the 27 (48%) abnormal tests in the carrier group were tritan defects and the remaining 14 (52%) were deutan defects. Nine of the 27 (33%) abnormals in the carrier group were identified as having bilateral defects. Six of these were deutan, and the remaining three were tritan dyschromatopsias. Only six of the 36 (16.66%) age matched controls were found to have any type of dyschromatopsia. Five (83.3%) of these were deutan defects. The remaining one was a tritan defect. The difference between the two groups using a χ2 test with one degree of freedom was statistically significant with a p value less that 0.001. Conclusions: Until now, LHON has always been characterised by a sudden, devastating vision loss. Asymptomatic carriers, those without vision loss, were considered unaffected by the disease. It now appears that asymptomatic carriers of the LHON mutation are affected by colour vision defects and may manifest other subtle, yet chronic, changes.

Headache in Idiopathic Intracranial Hypertension: Findings From the Idiopathic Intracranial Hypertension Treatment Trial

To characterize the phenotype, headache‐related disability, medical co‐morbidities, use of symptomatic headache medications, and headache response to study interventions in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT).

Adult learning principles and presentation pearls

Although lectures are one of the most common methods of knowledge transfer in medicine, their effectiveness has been questioned. Passive formats, lack of relevance and disconnection from the students needs are some of the arguments supporting this apparent lack of efficacy. However, many authors have suggested that applying adult learning principles (i.e., relevance, congruence with students needs, interactivity, connection to students previous knowledge and experience) to this method increases learning by lectures and the effectiveness of lectures. This paper presents recommendations for applying adult learning principles during planning, creation and development of lectures to make them more effective.

Headache attributable to disorders of the eye

Sensory innervation to the eye and periocular area arises from the ophthalmic branch of the trigeminal nerve. Thus, ocular, orbital, and systemic disorders may produce head pain with ocular signs and symptoms. Whereas some of these entities have characteristic diagnostic features, others mimic primary headache disorders such as migraine and cluster headache. This article reviews common ocular and neuro-ophthalmic conditions that are accompanied by pain in or near the eye.

Glaucoma detection and evaluation through pattern recognition in standard automated perimetry data

BackgroundPerimetry remains one of the main diagnostic tools in glaucoma, and it is usually used in conjunction with evaluation of the optic nerve. This study assesses the capability of automatic pattern recognition methods, and in particular the support vector machines (SVM), to provide a valid clinical diagnosis classification of glaucoma based solely upon perimetry data.MethodsOver 2,200 patient records were reviewed to produce an annotated database of 2,017 eyes. Visual field (VF) data were obtained with HFA II perimeter using the 24-2 algorithm. Ancillary information included treated and untreated intraocular pressure, cup-to-disk ratio, age, sex, central corneal thickness and family history. Ophthalmic diagnosis and classification of visual fields were provided by a consensus of at least two glaucoma experts. The database includes normal eyes, cases of suspect glaucoma, pre-perimetric glaucoma, and glaucoma with different levels of severity, as well as 189 eyes with neurologic or neuro-ophthalmologic defects. Support vector machines were trained to provide multi-level classifications into visual field and glaucoma diagnosis classes.ResultsNumerical validation indicates 70–90% expected agreement between multi-stage classifications provided by the automated system, using a hierarchy of SVM models, and glaucoma experts. Approximately 75% accuracy for the classification of glaucoma suspect and pre-perimetric glaucoma (which by definition do not exhibit glaucomatous defects) indicates the ability of the numerical model to discern subtle changes in the VF associated with early stages of glaucoma. The Glaucoma Likelihood Index provides a single number summary of classification results.ConclusionsAutomatic classification of perimetry data may be useful for glaucoma screening, staging and follow-up.