Bradley J. Katz

A Comparison of Idiopathic Intracranial Hypertension With and Without Papilledema

Objective.— To compare clinical features, visual characteristics, and treatment of idiopathic intracranial hypertension patients with and without papilledema.

Anemia and papilledema

PURPOSE To elucidate the relationship between anemia and raised intracranial pressure (ICP). DESIGN Interventional case series. METHODS Retrospective case series and review of the literature. Only patients with documented papilledema, neuroimaging ruling out a space-occupying lesion, and anemia were included. RESULTS Five women with confirmed idiopathic intracranial hypertension (IIH) (normal brain magnetic resonance imaging, normal cerebrospinal fluid, elevated intracranial pressure), and one man with presumed IIH (normal head computed tomography [CT], no lumbar puncture) were evaluated. All had bilateral papilledema associated with peripapillary hemorrhages. Two had retinal cotton-wool spots (CWS), and two had preretinal hemorrhages. All had severe iron deficiency anemia, which was discovered at the time of their ocular complaints in five of them. Their symptoms and signs improved dramatically after treatment of the anemia. We found 30 well-documented cases in the English and French literature. Among those, 13 were excluded from our analyses (11 had confounding disorders, and two had cerebral venous thrombosis). In the remaining 17 cases, isolated raised ICP associated with anemia was the most likely diagnosis, although in none of these cases was cerebral venous thrombosis excluded. CONCLUSIONS Anemia may play a role in the occurrence of raised ICP and papilledema. Although only a few cases in the literature support this association, it may be more common than previously thought. Because most patients are not known to be anemic when papilledema is discovered, we suggest that a complete blood count be obtained in patients with IIH, especially in the absence of known associated factors such as obesity or medications or when treatment aimed at lowering ICP fails to improve the patients symptoms. The underlying mechanisms remain unknown, but cerebral venous thrombosis should be carefully excluded.

Genetic association of LOXL1 gene variants and exfoliation glaucoma in a Utah cohort.

Exfoliation glaucoma (XFG) is the commonest identifiable cause of secondary open-angle glaucoma worldwide, characterized by the deposition of fibrillar proteins in the anterior segment of the eye. We investigated LOXL1 gene variants previously identified to confer susceptibility to exfoliation glaucoma (XFG) in a Utah Caucasian cohort. After a standard eye examination protocol we genotyped SNPs rs2165241 and rs3825942 in 62 XFG or XFS patients and 170 normal controls. Genotype frequency distribution, odds ratios (ORs), and population attributable risks were calculated for the risk alleles. The SNP rs2165241 was significantly associated with XFG and XFS (p=4.13x10-9 for an additive model, ORhet=4.42 (2.30-8.50), ORhom=34.19 (4.48-261.00); T allele: 83.1% in cases versus 52.4% in controls). Significant association was also found for rs3825942: (p=1.89x10-6). Our findings confirm genetic association of LOXL1 with XFG and XFS and implicate a potential role of cross linking of elastin in the pathogenesis of XFG. This information will potentially guide glaucoma monitoring efforts by targeting individuals whose genetic profiles put them at higher risk for XFG.

Retinol-binding protein and retinol analysis in cerebrospinal fluid and serum of patients with and without idiopathic intracranial hypertension.

Background: Several studies have implicated vitamin A-related compounds in the pathogenesis of idiopathic intracranial hypertension (IIH). The goal of this study was to compare cerebrospinal fluid (CSF) and serum concentrations of retinol and retinol-binding protein (RBP) in subjects with and without IIH. Methods: CSF and serum samples were collected from 87 subjects. The study population was composed of subjects with IIH (IIH group, n = 28), subjects with non-IIH neurologic conditions (neurology controls, n = 42), and subjects undergoing preoperative lumbar puncture but with no known neurologic conditions (anesthesia controls, n = 17). RBP levels (nM) were determined using radial immunodiffusion, and retinol levels (nM) were determined using high-performance liquid chromatography. Results: The retinol/RBP ratio was greater in CSF than in serum, especially in subjects with IIH. Conclusions: The finding of increased levels of unbound retinol in the CSF of subjects with IIH provides further evidence that vitamin A may be involved in the pathogenesis of IIH. Comparative statistical analyses revealed multivariate relationships that demonstrate the need to further investigate correlations between vitamin A and RBP levels in CSF and serum.

Optic atrophy and sensorineural hearing loss in a family caused by an R445H OPA1 mutation

Autosomal dominant optic atrophy (ADOA) is the most common form of inherited optic atrophy. Four genetic loci have been associated with ADOA: OPA1, OPA2, OPA3, and OPA4. Out of these four loci, only one gene has been identified, OPA1. We previously described a unique syndrome of optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia in two unrelated families associated with an R445H mutation in OPA1. The R445H mutation is the only OPA1 mutation that has been associated with this syndrome. In this manuscript, we clinically characterize an unrelated family with four members affected by optic atrophy and hearing loss without extraocular motility abnormalities or ptosis. This family also harbors the R445H mutation. These cases help illustrate the intra‐ and inter‐family variability in phenotype associated with this mutation. As we continue to learn more about OPA1 and the function of its protein product, we will begin to understand the pathophysiology of optic atrophy. This understanding will ultimately lead to novel treatments directed toward preventing the visual loss and disability associated with this inherited disease.

Progression from anomalous optic discs to visible optic disc drusen.

At age 5, a patient underwent fundus photography that disclosed elevated optic discs without drusen. A head computed tomography did not show optic nerve calcification. At age 9, no disc drusen were evident by ophthalmoscopy, but a CT now showed optic nerve calcification. At age 12, optic disc drusen were faintly evident on photographs; visual fields showed blind spot enlargement OD and an arcuate defect OS. At age 21, he had numerous discrete disc drusen in both eyes, disc pallor, and slight progression of the visual field defects. This case documents the progression from anomalous optic discs to ophthalmoscopically visible optic nerve drusen over a 16-year period.

CYP1B1 and MYOC Mutations in 116 Chinese Patients With Primary Congenital Glaucoma

OBJECTIVES To clinically characterize 116 Chinese patients with primary congenital glaucoma and to determine the role of CYP1B1 and MYOC mutations in this cohort. METHODS This study included 116 unrelated patients with primary congenital glaucoma and 120 ethnically matched, unrelated, healthy controls in China. CYP1B1 and MYOC were amplified from genomic DNA, followed by direct DNA sequencing to identify disease-causing variants. RESULTS Twenty patients (17.2%) had CYP1B1 mutations. Five of these patients had homozygous mutant alleles and 4 had compound heterozygous mutations. Fourteen of the mutations were novel. Three patients (2.6%) had MYOC mutations, all of which were novel. CONCLUSIONS This study describes the spectrum of CYP1B1 and MYOC mutations in a large cohort of Chinese patients with primary congenital glaucoma. The role of mutations in CYP1B1 and MYOC varies, depending on the ethnic origin of the patients. Clinical Relevance Patients with primary congenital glaucoma and CYP1B1 mutations tend to have a more severe phenotype than those without mutations. Genetic testing of CYP1B1 mutations may help predict new cases and their prognoses.

Persistent severe visual and electroretinographic abnormalities after intravenous Cisplatin therapy.

A 55-year-old man inadvertently received four times the intended dose of intravenous cisplatin as part of a chemotherapeutic salvage regimen for non-Hodgkin lymphoma. Immediately after treatment, he developed bilateral irreversible visual loss. Visual acuity was 20/300 in OU and visual fields showed central scotomas bilaterally. Although the fundus examination findings were normal, an electroretinogram showed markedly reduced a-wave amplitudes and absent b-waves. At autopsy 8 months later, photoreceptors appeared normal. Splitting of the outer plexiform layer was present, consistent with loss of the ERG b-wave. This is the first reported case of persistent visual loss from intravenous cisplatin toxicity and the first case to describe ocular histopathologic findings.

FL-41 Tint Improves Blink Frequency, Light Sensitivity, and Functional Limitations in Patients with Benign Essential Blepharospasm

OBJECTIVE The objective of these 2 studies was to assess the efficacy of FL-41-tinted lenses in the treatment of benign essential blepharospasm (BEB). DESIGN A randomized crossover study and a randomized crossover case-control study. PARTICIPANTS The first study included 30 subjects with BEB. The second study included 26 subjects with BEB and 26 controls. METHODS For the first study, subjects were randomized to wear either FL-41 or gray-tinted lenses for 2 weeks. After a 2-week washout period, the other lens was worn for 2 weeks. Questionnaires were completed at baseline, after the first lens, and after the second lens. In the second study, surface electromyography (EMG) was used to measure blink frequency, duration, and force while subjects read and wore FL-41, rose, or gray-tinted lenses. MAIN OUTCOME MEASURES Questionnaires were used to assess perceptions of light sensitivity and the effect of light sensitivity on activities of daily living (ADL). EMG was used to measure blink frequency, duration, and force. RESULTS Most participants observed improvement while wearing both FL-41 and gray-tinted lenses. FL-41-tinted lenses provided superior improvement in the areas of reading, fluorescent light sensitivity, overall light sensitivity, blepharospasm frequency, and blepharospasm severity. FL-41 lenses reduced mean blink rate compared with both rose and gray-tinted lenses, and reduced eyelid contraction force compared with rose-tinted lenses. CONCLUSIONS FL-41 lenses provided both subjective and objective benefit to subjects with BEB. Physicians should consider recommending this noninvasive and inexpensive lens tint to patients with BEB. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

A novel method for screening the multifocal electroretonogram in patients using hydroxychloroquine.

Purpose: To evaluate retinal function in patients on hydroxychloroquine using multifocal electroretinography. Methods: A retrospective chart review was performed for 23 patients (46 eyes) on hydroxychloroquine therapy and referred for multifocal electroretinogram (mfERG) testing. Duration of treatment, daily hydroxychloroquine dose, visual acuity, fundus examination, color vision testing, Amsler grid testing, visual field examination, and fluorescein angiography results were obtained when available. Multifocal electroretinogram response amplitudes were calculated for the central and paracentral regions and compared with previously published normal values. The central and paracentral regions of the mfERG color difference plot, which assigns colors to localized areas of the mfERG based on deviation from normal, were assessed using a novel Color Difference Plot Scoring System which relies on the color pattern observed within each region. Results: Ninety-two regions were assessed for response amplitudes, 31 of which showed a depressed response amplitude. Of the 17 eyes which had at least one region with a depressed response amplitude, clinical examination findings were relatively benign. Color difference plot scoring showed strong agreement with response amplitude, with a Color Difference Plot Scoring System score of 2 or 3 showing 93.55% sensitivity and 60% specificity for a depressed response amplitude. Interrater reliability of the scoring system as measured by Kendall’s W coefficient of concordance was 0.6484 (P < 0.00001). Conclusion: The mfERG appears to be able to detect decreased retinal function in hydroxychloroquine patients with normal clinical examinations, and may be useful in identifying patients that require close monitoring for the development of clinically relevant toxicity. The Color Difference Plot Scoring System may be used as a tool to aid in the interpretation of results of the mfERG in the clinic setting.