Michelle Y. Wang

Vitreo-papillary adhesion in macular hole and macular pucker.

Purpose: Vitreo-macular pathology may be influenced by vitreo-papillary adhesion (VPA). Optical coherence tomography/scanning laser ophthalmoscopy (OCT/SLO) was used to identify VPA in full-thickness macular hole, lamellar hole, and macular pucker (MP). Methods: Ultrasonography and OCT/SLO were performed in 55 subjects: 16 with macular hole, 11 with lamellar hole, and 28 with MP. The main outcome measures were the presence of posterior vitreous detachment by ultrasound, and the findings of VPA and intraretinal cysts by OCT/SLO. Results: Posterior vitreous detachment was detected by ultrasound in 26/28 (92.9%) eyes with MP, 6/11 (54.5%) eyes with lamellar hole (P < 0.05), and 4/16 (25%) eyes with macular hole (P < 0.00001). Optical coherence tomography/scanning laser ophthalmoscopy detected VPA in 14/16 (87.5%) macular hole eyes, 4/11 (36.4%) lamellar hole eyes (P < 0.05), and 5/28 (17.9%) MP eyes (P < 0.00005). Intraretinal cysts were present in 4/5 (80%) MP eyes with VPA but only 1/23 (4.3%) MP eyes without VPA (P < 0.005). Conclusion: Vitreo-papillary adhesion was significantly more common in full-thickness macular hole than lamellar hole or MP. When present in MP, VPA was frequently associated with intraretinal cysts. Hence, VPA may have an important influence on the vectors of force at the vitreo–retinal interface inducing holes and cysts.

Drug-related mitochondrial optic neuropathies.

Background: There is a group of optic neuropathies of either genetic or acquired origin characterized by similar clinical manifestations with preferential involvement of the papillomacular bundle (PMB). PMB fibers are most susceptible to injury as they are small, unmyelinated, and have high-energy demands. These optic neuropathies share a presumed common pathophysiology of mitochondrial dysfunction. Evidence Acquisition: A variety of medications cause optic neuropathy by interfering with mitochondrial function. The evidence linking these therapeutic agents as a cause of mitochondrial optic neuropathy (MON) is well established in some and less certain in others. The differential diagnosis includes other optic nerve disorders producing bilateral, symmetric visual loss, including certain nutritional deficiencies, toxins, and genetic diseases. Results: Ethambutol, chloramphenicol, linezolid, erythromycin, streptomycin, and antiretroviral drugs can cause drug-related MON. In many cases, drug toxicity is dose and duration dependent, and discontinuation of the drug in a timely manner can lead to significant visual recovery. Conclusions: Mitochondrial optic neuropathies are increasingly recognized as a spectrum of conditions that reach a similar end point by compromising a common pathway of mitochondrial dysfunction. Clinicians should be aware of drugs that can cause a MON. Prompt recognition of this association is critical in preventing irreversible, profound visual loss.

The Prevalence and Risk Indicators of Uncorrected Refractive Error and Unmet Refractive Need in Latinos: The Los Angeles Latino Eye Study

PURPOSE To determine the age- and sex-specific prevalence and risk indicators of uncorrected refractive error and unmet refractive need among a population-based sample of Latino adults. METHODS Self-identified Latinos 40 years of age and older (n = 6129) from six census tracts in La Puente, California, underwent a complete ophthalmic examination, and a home-administered questionnaire provided self-reported data on potential risk indicators. Uncorrected refractive error was defined as a >or=2-line improvement with refraction in the better seeing eye. Unmet refractive need was defined as having <20/40 visual acuity in the better seeing eye and achieving >or=20/40 after refraction (definition 1) or having <20/40 visual acuity in the better seeing eye and achieving a >or=2-line improvement with refraction (definition 2). Sex- and age-specific prevalence and significant risk indicators for uncorrected refractive error and unmet refractive need were calculated. RESULTS The overall prevalence of uncorrected refractive error was 15.1% (n = 926). The overall prevalence of unmet refractive need was 8.9% (n = 213, definition 1) and 9.6% (n = 218, definition 2). The prevalence of uncorrected refractive error and either definition of unmet refractive need increased with age (P < 0.0001). No sex-related difference was present. Older age, <12 years of education, and lack of health insurance were significant independent risk indicators for uncorrected refractive error and unmet refractive need. CONCLUSIONS The data suggest that the prevalence of uncorrected refractive error and unmet refractive need is high in Latinos of primarily Mexican ancestry. Better education and access to care in older Latinos are likely to decrease the burden of uncorrected refractive error in Latinos.

Ethambutol optic neuropathy: how we can prevent 100,000 new cases of blindness each year.

E thambutol is the most common and extensively studied cause of optic nerve toxicity. Drug-resistant strains of tuberculosis often necessitate use of this antibiotic. The World Health Organization estimates that there are about 9.2 million new cases of tuberculosis each year (1). About 55% of these patients take ethambutol each year as a treatment for tuberculosis or Mycobacterium avium (1). If we take the conservative estimate that 2% (2) of these individuals will experience significant and irreversible visual loss, then the annual incidence of this serious iatrogenic complication is 100,000. In this issue of the Journal of Neuro-Ophthalmology, Eun Ji Lee et al (3) report a retrospective analysis of 857 patients who had been given ethambutol in Korea. In this cohort, 89 (10%) complained of visual symptoms. By the authors entry criteria, only 13 (1.5%) were determined to have optic neuropathy attributable to ethambutol. These 13 patients received average daily doses of 18 mg/kg—well within recommended dosage limits—and lost vision after an average of 7 months, findings that are consistent with previous reports (4). Only one third of the patients recovered vision over a period of approximately 5 months. With regard to risk factors for the development of the optic neuropathy, the authors found renal dysfunction and daily dose levels to be important. They concluded that the cumulative dose did not significantly contribute to visual loss, but only 3 patients took the medication long enough to reach a P < 0.05 significance level. The authors found that renal function, as demonstrated by glomerular filtration rate, was an important risk factor. This finding is not surprising, given that ethambutol is largely cleared by the kidney. In the personal experience of one of us (AAS), almost every case of ethambutol optic neuropathy involves one or more of the following factors: 1) the patient has been given too large a dose, often because low weight has not been taken into account; 2) the patient has documented poor renal function, and 3) declining renal function with age has not been considered. Although ethambutol optic neuropathy is the exemplar of toxic optic neuropathies, streptomycin, chloramphenicol, and linezolid produce similar clinical manifestations. The patient develops slowly progressive loss of visual acuity in conjunction with central or cecocentral scotomas, dyschromatopsia, and loss of high spatial frequency contrast sensitivity (5). These psychophysical features are explained by selective damage to the papillomacular bundle. Optical coherence tomography (OCT) confirms axon loss, and fundus examination shows optic disc pallor that is most pronounced on the temporal side. Nutritional disorders such as folic acid or vitamin B12 deficiency, and combinations of toxicity and nutritional disorders such as tobacco-alcohol amblyopia and the Cuban epidemic of optic neuropathy produce similar clinical manifestations (6), as do inborn errors of metabolism due to mitochondrial or somatic DNA mutations such as Leber hereditary optic neuropathy (LHON) and autosomal dominant (OPA-1) optic neuropathy (6).

Abnormalities of the optic disc.

The optic disc represents the anterior end of the optic nerve, the most forward extension of the central nervous system (CNS). The optic disc gives a rare glimpse into the CNS. Hence, diseases of the CNS are often manifested on fundus examination. Abnormalities of the optic disc may reflect eye disease (such as glaucoma), problems in development (as in various syndromes), or CNS disease (such as increased intracranial pressure). Each optic nerve is composed of about 1.2 million axons deriving from the retinal ganglion cells of one eye. Optic atrophy is a morphological sequela reflecting the loss of many or all of these axons. Myriad diseases such as hereditary, metabolic, tumor, and increased intracranial pressure can lead to optic atrophy. Some diseases, such as optic disc drusen, intracranial masses, orbital tumors, ischemic optic neuropathies, inflammations, and infiltrations, can produce optic disc edema before leading to optic atrophy. A number of new imaging modalities, such as optical coherence tomography (OCT), quantitate the thickness of the peripapillary retinal nerve fiber layer as an indirect measure of axonal loss or swelling. OCT can therefore be used to quantitate pathology or the response to therapy in various generalized CNS conditions, such as multiple sclerosis.

Axonal degeneration in peripheral nerves in a case of Leber hereditary optic neuropathy.

Background: Leber hereditary optic neuropathy (LHON) is a mitochondrial DNA (mtDNA) genetic disorder characterized by profound bilateral loss of central vision due to selective loss of retinal ganglion cells. Most patients with LHON do not have complaints related to the peripheral nervous system. We investigated possible qualitative and quantitative histological changes in the peripheral nerve of a patient with LHON as compared to normal controls. Methods: Brachial plexus specimens were obtained at necropsy from a patient with LHON carrying the 3460/ND1 mtDNA mutation and age-matched controls without known history of neurological disease. The nerves were evaluated by light microscope coupled to a digital camera-based morphometric analysis and electron microscopy. Results: Extensive axonal degeneration of the large heavily myelinated fibers was found in the brachial plexus from the patient with LHON. In LHON nerve fascicles, we counted over 10 times as many degenerated profiles as found in the control nerve fascicles. Conclusions: Microscopic examination of the brachial plexus in the patient with LHON clearly demonstrated a significant pattern of neurodegeneration. Our study suggests that peripheral neuropathy may be a subclinical feature associated with LHON.

Visual improvement with the use of idebenone in the treatment of Wolfram syndrome.

R ecently in the Journal of Neuro-Ophthalmology, we discussed the potential efficacy of idebenone, a coenzyme Q derivative that acts as a carrier in the mitochondrial electron transport chain, in treating patients with Leber hereditary optic neuropathy (LHON) (1). Within the past 2 decades, Wolfram syndrome (WS) has been mapped to chromosome 4p16.1 (2) and is thought to harbor a mitochondrial genome deletion (3,4) or complex III deficiency (5). The only current treatment for this devastating disease is limited to blood sugar control with lower doses of insulin compared with patients with diabetes mellitus (DM). We had the opportunity to treat a patient with WS with idebenone, hoping for improvement in visual function. A 21-year-old Romanian man was initially evaluated 5 years previously with progressive bilateral visual and hearing loss and a neurogenic bladder. Surgical history was significant for bilateral cataract extractions with intraocular lens implants at 11 years of age. Medications included insulin and effexor. Family history was significant for DM in both parents, without a history of hearing or visual loss. Genetic testing confirmed the diagnosis of WS with the mutation of the WFS1 Wolframin gene. The patient was overweight but appeared younger than his stated age. Visual acuity was light perception to bare hand motion bilaterally. Pupils were sluggishly reactive without a relative afferent pupillary defect. Intraocular pressures were normal and funduscopy revealed bilateral optic disc pallor (Fig. 1). Spectral domain optical coherence tomography (OCT) showed marked thinning of the retinal nerve fiber layer in each eye (Fig. 2). The patient had bilateral sensorineural hearing loss of higher frequency sounds with preservation of hearing lower frequencies. He was prescribed idebenone that was gradually increased from 150 mg daily to 150 mg twice a day at 2 months, and then to 150 mg 3 times a day at 4 months. At 3 months, the patient’s vision improved to hand motions at 1 foot bilaterally. At 6 months, visual acuity was hand motions at 2 feet, right eye, and hand motions at 4 feet, left eye. Ophthalmoscopic and OCT findings remained unchanged. Our patient had difficulty with standard kinetic visual field testing given his poor vision (Fig. 3). To enhance light intensity of the stimulus, we used green and red laser stimuli rather than white. We were able to quantitate the visual field using a kinetic technique with these colored stimuli (Fig. 2). The patient could see the brighter more intense green stimulus, with some false positives with the red stimulus, whereas he previously was unable to detect any such stimulus on visual field testing. Recent publications describe the use of idebenone, a coenzyme Q10 derivative, in the treatment of LHON (1,7,8). Given that WS has features of mitochondrial dysfunction, we decided to initiate idebenone treatment. In our patient, idebenone resulted in progressive but subjective visual recovery at 6 months. Similarly, in reports of response to idebenone in LHON, the effects usually do not begin until after 6 months (1,7). This long-term

A compact neural network for partial-response maximum-likelihood detectors: algorithmic study

A compact neural network algorithm for partial-response maximum-likelihood (PRML) sequence detection is presented. Compact neural networks are a class of locally connected neural networks suitable for very large scale integration (VLSI) implementation. The hardware complexity for VLSI implementation of the proposed algorithm grows linearly with the level of the deliberately designed symbol interference effects of the partial-response (PR) signalling scheme. Large dedicated memory for storage of likelihood matrices in digital Viterbi-algorithm-based detectors is not needed for the proposed detector. Detailed analysis on network stability for network topology and time constant of an analog neuron is described. This detector algorithm has competitive bit-error rate performance when compared with the digital Viterbi algorithm under the noise condition for many real-world applications. The proposed algorithm is suitable for analog VLSI implementation because of its low time complexity and linear area complexity for the detection of PRML signalling schemes.

Headache and whiteout vision as the presenting symptoms in a case of Takayasu retinopathy.

PURPOSE To report a case of Takayasu retinopathy presenting as chronic headache and whiteout of vision. METHODS A case report of a 28-year-old woman with no medical history diagnosed with Takayasu retinopathy after a complete ophthalmologic examination, including widefield fluorescein angiography. RESULTS Dilated fundus examination revealed sharp margins in both eyes and mildly attenuated arterioles and distended veins. The peripheral examination was significant for several white-centered intraretinal hemorrhages. A widefield fluorescein angiogram showed numerous small microaneurysms in the periphery. A computer tomography angiogram of the chest showed central wall thickening of the aortic arch, proximal branch vessels of the aortic arch, including left common carotid and right common carotid, and middle lower lobe of the right pulmonary artery, all of which were consistent with the diagnosis of Takayasu disease. The patient underwent cardiovascular bypass surgery and her ocular symptoms resolved. CONCLUSION Up to one third of patients with Takayasu disease experience visual disturbances, and as a result, ophthalmologists may be the first physicians to encounter and diagnose this condition. The various stages of Takayasu retinopathy are characterized by dilation of small vessels, capillary microaneurysm formation, and development of arterial-venous anastomoses. The initial clinical presentation of Takayasu disease can be varied and nonspecific, therefore a high index of clinical suspicion is essential for diagnosis.

Architecture and Design of 1-D Enhanced Cellular NeuralNetwork Processors for Signal Detection

One-dimensional cellular array processor architecture and design for neural-based partial response (PR) signal detection are presented. Analog parallel computing approaches have many attractive advantages in achieving low power, low cost, and faster processing speed by its uniquely coupled parallel and distributed processing nature. In this paper, we describe the maximum likelihood sequence estimation (MLSE) algorithm for PR signals, the enhanced Cellular Neural Network (CNN) processor array architecture to realize the detection algorithm, and system performance evaluation. Analytical models and simulations on a design example of the detector have been employed to demonstrate the advantages of this scalable VLSI architecture. A processing rate of 265 Mbps was achieved for a prototype detector on a silicon area of 5.14 mm by 5.81 mm is a 1.2 µm CMOS technology. The processing rate can be beyond 1Gbps if it is implemented in the same amount of silicon area by using 0.5 µm CMOS technology. Such promising results clearly demonstrate the ability to meet the needs in future high speed data communication by VLSI realization of maximum likelihood sequence detectors based on the enhanced cellular neural network paradigm.