PURPOSE OF REVIEW: The purpose of this study is to review commonly encountered adverse ocular effects of illicit drug use. RECENT FINDINGS: Drug and alcohol abuse can produce a variety of ocular and neuro-ophthalmic side effects. Novel, so-called 'designer', drugs of abuse can lead to unusual ocular disorders. Legal substances, when used in manners for which they have not been prescribed, can also have devastating ophthalmic consequences. SUMMARY: In this review, we will systematically evaluate each part of the visual pathways and discuss how individual drugs may affect them.
Purpose of review: To discuss recent advances in potential treatments for Leber hereditary optic neuropathy (LHON), a typically visually devastating hereditary optic neuropathy caused by mutations in the mitochondrial genome.
Recent findings: Idebenone has been proposed as a means of bypassing defective complex I activity and a free radical scavenger to prevent oxidative damage. EPI-743 may have more potency than idebenone, but no clinical trials have been performed. Gene therapy techniques have advanced significantly, including allotopic expression and nuclear transfer. Successful rescue of animal models of LHON with both of these therapies has been demonstrated. Introduction of exogenous DNA into the mitochondrial genome with mitochondrial targeting of viral vectors is another promising technique.
Summary: There are currently no proven treatments for LHON. However, there are many promising novel treatment modalities that are currently being evaluated, with several clinical trials underway or in the planning stages. Supportive measures and genetic counseling remain of great importance for these patients.
Background: Optic atrophy may be the sequela of optic nerve injury due to any insult, including isolated and syndromic genetic diseases. Alanyl-tRNA synthetase 2 (AARS2) pathogenic variants have been reported to cause leukodystrophy with ovarian failure, and cardiomyopathy (#615889) as well as combined oxidative phosphorylation deficiency-8 (#614096). We report a young child who presented with decreased vision due to optic atrophy and was found to harbor missense variants in the AARS2 gene expanding the phenotypic expression of the AARS2 gene.Materials and Methods: Single observational case report with genetic testing, laboratory testing, neurologic and ophthalmic clinical examinations, and neuroimaging performed at a tertiary academic medical center.Results: An 18-month old Korean boy was noted to have a progressive decline in visual function. The physical exam revealed bilateral optic atrophy, peripheral retinal bone spicule pigmentation, and absent patellar reflexes. Electromyography was consistent with demyelinating polyneuropathy. Magnetic resonance imaging (MRI) of the brain and spine showed cerebellar and supratentorial white matter multifocal changes with areas of restricted diffusion, and dorsal column signal abnormalities. Whole exome sequencing revealed two missense variants in the AARS2 gene [c.1519G>C (p.V507L) and c.2165G>A (p.R722Q)], found to be in trans on parental testing.Conclusions: Missense variants in the AARS2 gene are the likely cause of the retinopathy and optic atrophy in this patient. This finding expands the phenotypic spectrum of the AARS2 gene.
Purpose:
Titmus stereoacuity testing has been used to estimate visual acuity in the evaluation of non-organic visual loss. Previous predictions were derived from optical degradation of visual acuity in normal subjects and may not account for the variability seen in patients with neuro-ophthalmic pathologies included in the differential diagnosis of non-organic visual loss. The purpose of this study was to evaluate the relationship between Titmus stereoacuity and minimal visual acuity based on a real-world testing environment.
Design:
Cross-sectional, observational study.
Subjects:
All patients presenting to our neuro-ophthalmology service between 4/25/2014 and 7/31/2014.
Methods:
All subjects underwent routine neuro-ophthalmic examination, including Titmus stereoacuity measurements. A compound Bayesian logit-lognormal model accounting for heteroskedasticity was used to determine 95% and 99% prediction intervals of the worse eye’s near visual acuity based on stereoacuity. LogMAR acuity and log stereoacuity were analyzed.
Main Outcome Measures:
Titmus stereoacuity and worse eye visual acuity.
Results:
Of 561 patients, 364 subjects aged 11 to 91 years were included. Titmus stereoacuity was positively associated with VA: 9 circles correct (40 seconds of arc) indicated visual acuity of at least 20/40 with 95% confidence and 20/79 with 99% confidence; 6 circles correct (80 seconds of arc): 20/62 and 20/180, respectively; and 4 circles correct (140 seconds of arc): 20/110 and 20/570, respectively.
Conclusions:
When fully accounting for individual variation and the full spectrum of neuro-ophthalmic diseases affecting visual acuity, stereoacuity remains associated with visual acuity, but previous commonly-used visual acuity estimates based on stereoacuity overestimated visual acuity. Our results more accurately predict minimum visual acuity from Titmus stereoacuity and should be preferentially used when evaluating patients with suspected non-organic visual loss. We demonstrate that Titmus stereoacuity cannot definitively prove normal visual acuity, and therefore can suggest, but not fully establish, the diagnosis of non-organic visual loss.
Importance: Diagnostic errors can lead to the initial misdiagnosis of optic nerve sheath meningiomas (ONSM), which can lead to vision loss.
Objective: To identify factors contributing to the initial misdiagnosis of ONSM.
Design, Setting, and Participants: We retrospectively reviewed 35 of 39 patients with unilateral ONSM (89.7%) who were seen in the tertiary neuro-ophthalmology practice at Emory University School of Medicine between January 2002 and M
arch 2017. The Diagnosis Error Evaluation and Research taxonomy tool was applied to cases with missed/delayed diagnoses.
Exposures: Evaluation in a neuro-ophthalmology clinic.
Main Outcomes and Measures: Identifying the cause of diagnostic errors for patients who initially received a misdiagnosis who were found to have ONSM.
Results: Of 35 patients with unilateral ONSM (30 women [85.7%]; mean [SD] age, 45.26 [15.73] years), 25 (71%) had a diagnosis delayed for a mean (SD) of 62.60 (89.26) months. The most common diagnostic error (19 of 25 [76%]) was clinician assessment failure (errors in hypothesis generation and weighing), followed by errors in diagnostic testing (15 of 25 [60%]). The most common initial misdiagnosis was optic neuritis (12 of 25 [48%]), followed by the failure to recognize optic neuropathy in patients with ocular disorders. Five patients who received a misdiagnosis (20%) underwent unnecessary lumbar puncture, 12 patients (48%) unnecessary laboratory tests, and 6 patients (24%) unnecessary steroid treatment. Among the 16 patients who initially received a misdiagnosis that was later correctly diagnosed at our institution, 11 (68.8%) had prior magnetic resonance imaging (MRI) results that were read as healthy; 5 (45.5%) showed ONSM but were misread by a non-neuroradiologist and 6 (54.5%) were performed incorrectly (no orbital sequence or contrast). Sixteen of the 25 patients (64%) had a poor visual outcome.
Conclusions and Relevance: Biased preestablished diagnoses, inaccurate funduscopic examinations, a failure to order the correct test (MRI brain/orbits with contrast), and a failure to correctly interpret MRI results were the most common sources of diagnostic errors and delayed diagnosis with worse visual outcomes and increased cost (more visits and tests). Easier access to neuro-ophthalmologists, improved diagnostic strategies, and education regarding neuroimaging should help prevent diagnostic errors..