Purpose
To analyze mitochondrial DNA (mt DNA) gene mutations in a 19-year-old female patient, who presented with chronic progressive external ophthalmoplegia (CPEO), together with her mother and younger sister.
Methods
The diagnosis of mitochondrial myopathy was made based on clinical and biologic analysis. Histochemical methods were used to detect ragged-red fibers (RRFs) and ragged-blue fibers (RBFs) on a muscle biopsy of the patient. All mitochondrial gene DNA fragments of the patient, her mother, and younger sister were amplified by polymerase chain reaction. The products were sequenced and compared with reference databases.
Results
A novel T1658C mutation and a known A10006G mutation were identified in the mitochondrial tRNAVal gene and the tRNAGly gene, respectively, in the patient, her mother, and younger sister. The T1658C mutation changes the T loop structure of mitochondrial tRNAVal and the A10006G mutation disturbs the D loop of mitochondrial tRNAGly.
Conclusions
The T1658C and A10006G mutations of mtDNA may be responsible for the pathogenesis of the patient with CPEO.
Cyclic AMP signaling pathways play crucial roles in photoreceptor cells and other retinal cell types. Previous studies demonstrated a circadian rhythm of cyclic AMP level in chick photoreceptor cell cultures that drives the rhythm of activity of the melatonin synthesizing enzyme arylalkylamine N-acetyltransferase (Ivanova and Iuvone, 2003a) and the rhythm of affinity of the cyclic nucleotide-gated channel for cyclic GMP (Ko et al., 2004). Here we report that the photoreceptor circadian clock generates a rhythm in Ca2+/calmodulin-stimulated adenylyl cyclase activity, which accounts for the temporal changes in the cyclic AMP levels in the photoreceptors. The circadian rhythm of cyclic AMP in photoreceptor cell cultures is abolished by treatment with the L-type Ca2+ channel antagonist nitrendipine, while the Ca2+ channel agonist, Bay K 8644, increased cyclic AMP levels with continued circadian rhythmicity in constant darkness. These results indicate that the circadian rhythm of cyclic AMP is dependent, in part, on Ca2+ influx. Photoreceptor cell cultures exhibit a circadian rhythm in Ca2+/calmodulin-stimulated adenylyl cyclase enzyme activity with high levels at night and low levels during the day, correlating with the temporal changes of cyclic AMP in these cells. Both of the Ca2+/calmodulin-stimulated adenylyl cyclase genes, type 1 and type 8 (Adcy1 and Adcy8), displayed significant daily rhythms of mRNA expression under a light-dark cycle, but only the Adcy1 transcript rhythm persisted in constant darkness. Similar rhythms of Adcy1 mRNA level and Ca2+/calmodulin-stimulated adenylyl cyclase activity were observed in retinas of 2 week old chickens. These results indicate that a circadian clock controls the expression of Adcy1 mRNA and Ca2+/calmodulin-stimulated adenylyl cyclase activity; and calcium influx into these cells gates the circadian rhythm of cyclic AMP, a key component in the regulation of photoreceptor function.
Susac syndrome features the triad of multiple branch retinal artery occlusions, hearing loss due to microinfarctions of the cochlea, and encephalopathy due to brain microangiopathy. Initial misdiagnosis as multiple sclerosis (MS) is not uncommon. Magnetic resonance imaging evidence of microinfarctions of the corpus callosum and multiple yellow retinal arterial wall plaques on fundus examination are helpful in differentiating this condition from demyelinating diseases.
We describe a patient initially diagnosed as having MS who, after treatment with interferon beta-1a, was found to have multiple branch retinal artery occlusions. After interferon beta-1a cessation, rapid improvement of his visual fields and fluorescein angiographic appearance suggested that the interferon beta-1a may have exacerbated the retinal findings of Susac syndrome.
A 40 year-old Caucasian male, status post radial keratotomy OU in 1993, suffered pain, extreme photophobia, and mild loss of uncorrected visual acuity in the right eye after being struck by a nail. The patient presented with a small deep stromal lesion and was initially treated with a variety of antibiotic regimens without improvement in the lesion’s appearance. Upon referral the patient had confocal microscopy performed, which clearly demonstrated epithelial cells in the deep stroma and on the endothelial surface. Upon cessation of all medications the patient’s mild symptoms resolved, and his clinical appearance has remained stable without intervention for 9 months. Patients with radial keratotomy incisions are at risk for traumatic epithelial downgrowth even many years after surgery. Confocal microscopy can make the definitive diagnosis of epithelial downgrowth. Management of this condition remains controversial.
We present a 56 year-old, right-handed, congenitally deaf, female who exhibited a partial Balint's syndrome accompanied by positive visual phenomena restricted to her lower right visual quadrant (e.g., color band, transient unformed visual hallucinations). Balint's syndrome is characterized by a triad of visuo-ocular symptoms that typically occur following bilateral parieto-occipital lobe lesions. These symptoms include the inability to perceive simultaneous events in one's visual field (simultanagnosia), an inability to fixate and follow an object with one's eyes (optic apraxia), and an impairment of target pointing under visual guidance (optic ataxia). Our patient exhibited simultanagnosia, optic ataxia, left visual-field neglect, and impairment of all complex visual-spatial tasks, yet demonstrated normal visual acuity, intact visual-fields, and an otherwise normal neurocognitive profile. The patient's visuo-ocular symptoms were noticed while she was participating in rehabilitation for a small right pontine stroke. White matter changes involving both occipital lobes had been incidentally noted on the CT scan revealing the pontine infarction. As the patient relied upon sign language and reading ability for communication, these visuo-perceptual limitations hindered her ability to interact with others and gave the appearance of aphasia. We discuss the technical challenges of assessing a patient with significant barriers to communication (e.g., the need for a non-standardized approach, a lack of normative data for such special populations), while pointing out the substantial contributions that can be made by going beyond the standard neuropsychological test batteries.
Vision begins when light is absorbed by visual pigments. It is commonly believed that the absorption spectra of visual pigments are modulated by interactions between the retinal and amino acids within or near 4.5 Å of the retinal in the transmembrane (TM) segments. However, this dogma has not been rigorously tested. In this study, we show that the retinal-opsin interactions extend well beyond the retinal binding pocket. We found that, although it is positioned outside of TM segments, the C-terminus of the rhodopsin in the rockfish longspine thornyhead (Sebastolobus altivelis) modulates its λmax by interacting mainly with the last TM segment. Our results illustrate how amino acids in the C-terminus are likely to interact with the retinal. We anticipate our analyses to be a starting point for viewing the spectral tuning of visual pigments as interactions between the retinal and key amino acids that are distributed throughout the entire pigment.
Objective: To design a simple matching acuity test based on hand gestures that is minimally dependent on familiarity with symbols and letters. The visual acuity results obtained from children using the Handy Eye Chart™ were compared with results obtained with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart.
Design: Evaluation of diagnostic test or technology.
Participants: 60 children between 6 and 16 years of age were recruited consecutively from the Pediatric Ophthalmology section of the Emory Eye Center.
Methods: Monocular visual acuity was tested using both the new eye chart and the ETDRS chart, alternating the order of administration between subjects. Testing was performed on the subject’s eye with the poorest acuity.
Main Outcome Measures: Outcome measures were monocular logarithm of the minimum angle of resolution (logMAR) visual acuity scores for each chart.
Results: The acuities were shown to have a strong linear correlation (r = 0.95) and a mean difference in acuity of −0.03 (95% confidence interval −0.05 to −0.01) logMAR, equivalent to approximately 1.5 letters, with the new eye chart underestimating the vision as determined by the ETDRS chart. The 95% limits of agreement were ±1.6 lines.
Conclusion: The present study supports the validity of the new eye chart as a measure of visual acuity in pediatric patients ages 6 to 18 with vision ranging from 20/16 to 20/200.
Purpose.
Although diabetic retinopathy (DR) is clinically diagnosed based on vascular pathology, diabetic patients with angiographically normal retinas have been found to exhibit subtle defects in vision. This has led to the theory that diabetes-associated metabolic abnormalities directly impair neural retinal function before the development of vasculopathy, thereby resulting in visual deficits. In this study, we sought to delineate the temporal relationship between retinal dysfunction and visual deficits in a rat model of Type 1 diabetes. Moreover, we investigated the relative contribution of retinal dysfunction versus diabetes-induced lens opacity, to the visual deficits found in early-stage DR.
Methods.
Pigmented Long Evans rats were rendered diabetic with streptozotocin (STZ). Control and diabetic rats were assessed across 12 weeks of hyperglycemia for visual function with optokinetic tracking weekly visual acuity and monthly contrast sensitivity, retinal function with dark-adapted electroretinograms (monthly electroretinograms [ERGs]), and cataract formation with slit lamp exam (biweekly).
Results.
Diabetic rats exhibited significantly reduced visual function and delayed ERG responses by 1 month post-STZ. Significant cataracts did not develop until 6 weeks post-STZ. Moreover, increases in lens opacity (r = −0.728) and ERG implicit times (r = −0.615 for rod-dominated response and r = −0.322 for rod/cone mixed response) showed significant correlations with reductions in visual acuity in diabetic rats.
Conclusions.
STZ-induced hyperglycemia reduces visual function, affecting both visual acuity and contrast sensitivity. The data suggest that visual defects found in early-stage DR may initially involve abnormalities of the neural retina and worsen with later development of cataracts.
Purpose: To study the effect of flap thickness on visual acuity and refractive outcomes after laser in situ keratomileusis (LASIK) using 2 blade types with a mechanical microkeratome.
Setting: Emory Vision, Atlanta, Georgia, USA.
Methods: This retrospective analysis was of LASIK cases performed between January 2005 and June 2006 using an Amadeus I microkeratome and an ML7090 CLB blade (blade A) or a Surepass blade (blade B). Outcomes analyzed included flap thickness, uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction spherical equivalent (MRSE), the enhancement rate, and surgical complications 3 months postoperatively.
Results: Two hundred sixty-three eyes of 153 patients were analyzed; blade A was used in 158 eyes and blade B, in 105 eyes. The mean flap thickness was significantly thinner with blade A than with blade B (107 μm ± 12 [SD] versus 130 ± 20 μm) (P<.0001). There was no overall correlation with either blade between flap thickness and UDVA, CDVA, or MRSE (all r<0.2). At 3 months, there was no statistically significant difference in UDVA, CDVA, or MRSE between the 2 blade groups at 3 months (all P > .10), and there was no difference in the complication rates.
Conclusion: Flap thickness did not affect visual or refractive outcomes with a mechanical micro-keratome with either blade type.
Financial Disclaimer: No author has a financial or proprietary interest in any material or method mentioned.
An 80-year-old white woman with a history of hyperthyroidism treated with radioactive iodine ablation, gastroesophageal reflux disease complicated by Barrett esophagus, osteoarthritis, breast cancer status post-bilateral mastectomy, and diverticulosis presented with severe left-sided headache and diplopia. Three weeks prior to presentation, she developed a sharp pain located over the left temporal, parietal, and occipital regions. It was associated with exquisite scalp tenderness. Over the next few days, the pain progressed, involving the left side of the face, including the periorbital region. There was no radiation of the pain, and she had little relief with over-the-counter acetaminophen. She also experienced earache, sore throat, and left jaw pain with mastication.