North Carolina Macular Dystrophy: Long-term Follow-up of the Original Family.

PURPOSE: The phenotype of North Carolina macular dystrophy (NCMD) is highly variable and remains poorly appreciated and understood, often causing misdiagnoses in isolated cases. One of the features of NCMD is the general lack of progression despite its original name, "dominant progressive foveal dystrophy," as reported in 1971 by Lefler et al (W.H.L.). The purpose of this study was to report the long-term follow-up of this condition. DESIGN: Systematic, longitudinal, and detailed documentation along with the imaging of the peripheral retina. SUBJECTS: We reexamined 27 of the original family members with NCMD in an office setting 30 to 50 years after they were first reported. METHODS: The evaluation of all the affected subjects included best-corrected visual acuity (BCVA), slit-lamp and dilated-fundus examinations, wide-field fundus and autofluorescent photography, and spectral-domain OCT (SD OCT). Blood was collected for DNA extraction, banking, and sequencing. MAIN OUTCOME MEASURES: Best-corrected visual acuity, slit-lamp and dilated-fundus examinations, wide-field fundus and autofluorescent photography, and SD OCT. RESULTS: The 27 subjects examined were a part of the original family with NCMD that was initially reported in 1971. A point mutation (NC_000006.11:g.100040906G>T) (Hg19) in a noncoding region of a deoxyribonuclease I hypersensitivity binding site was found in all the affected subjects. Nine subjects were the affected children of those originally examined 30 to 50 years ago by Kent W. Small (K.W.S.) and W.H.L., and the remaining 17 subjects (34 eyes) had been examined 30 years previously by K.W.S. Of these 17 subjects (34 eyes), 4 of 34 (11%) eyes showed worsening of vision and evidence of fibrosis due to choroidal neovascular membranes (CNVMs). Fourteen of the 27 (51%) patients showed peripheral retinal drusen, which did not seem to correlate with the severity of the macular disease. CONCLUSIONS: Most patients with NCMD have stable vision and fundus findings throughout their lives. The ones who experienced BCVA decline did so because of the apparent evidence of CNVMs. Patients with grade 2 NCMD seem to be at an increased risk of further or progressive vision loss due to CNVMs. Intravitreal therapy with vascular endothelial growth factor inhibitors may benefit these patients if they are treated in a timely fashion. Peripheral retina drusen of varying degrees of severity were found in slightly more than half of the affected subjects.

Best Vitelliform Macular Dystrophy (BVMD) is a phenocopy of North Carolina Macular Dystrophy (NCMD/MCDR1).

PURPOSE: North Carolina Macular Dystrophy (NCMD) and Best Vitelliform Macular Dystrophy (BVMD) are rare autosomal dominant macular dystrophies. Both BVMD and NCMD have markedly variable expressivity. In some individuals, it can be difficult to differentiate between the two disease entities. METHODS: Clinical findings including fundus photography, fundus autofluorescence (FAF), and spectral domain optical coherence tomography (SD-OCT) were evaluated in 5 individuals with NCMD and 3 with BMD. Electrooculography (EOG) was performed in 2 NCMD subjects. Molecular diagnosis was performed using Sanger DNA sequencing. IRB approval was obtained. RESULTS: Five NCMD subjects had clinical findings indistinguishable from three of our BVMD subjects. Molecular diagnosis was confirmed in all but one BVMD subject who had an abnormal EOG prior to discovery of the BEST1 gene. Two NCMD subjects had an abnormal EOG with a normal ERG, which has been considered a unique feature of BVMD. SD-OCT in one BVMD subject demonstrated a small lucency/excavation into the choroid similar to that in grade 3 lesions of NCMD. Two NCMD subjects had elevated sub-macular lesions giving a pseudo-vitelliform appearance on OCT similar to BVMD. CONCLUSION: Best Vitelliform Macular Dystrophy can be a phenocopy of NCMD. There is considerable clinical overlap between NCMD and BVMD, which can cause diagnostic inaccuracies. Our new findings demonstrate that like BVMD, NCMD can also have an abnormal EOG with a normal ERG. The overlapping phenotypes of BVMD with NCMD may provide insights into the mechanisms of the macular changes.

Emerging therapeutics in Huntington's disease.

INTRODUCTION: Huntington's disease is a neurodegenerative disease that is characterized by motor dysfunction, behavioral/psychiatric symptoms, and cognitive impairment. Because of the lack of availability of curative or disease modifying treatments, much of clinical practice in HD care to date has focused on symptomatic treatment. Recent work has created optimism surrounding possible emerging disease modifying therapeutics. HD is a developing therapeutic field with diverse and promising emerging therapies. AREAS COVERED: A PubMed literature review was completed to discover pertinent reviews and analyses. ClinicalTrials.gov was referenced to find updated information about ongoing and planned trials. Lastly, because of the rapidly evolving nature of HD treatments, drug manufacturer websites and press releases were reviewed to provide current information surrounding recently reported trial results. EXPERT OPINION: Recent setbacks involving antisense oligonucleotide research should not diminish enthusiasm and hope for the many other novel therapies currently being pursued. We remain optimistic about the many promising emerging therapies for HD, and we expect that growing knowledge about the pathophysiology of the underlying disease and constant advances in biotechnology will lead to therapies that have a meaningful impact in the lives of patients, their families, and those who care for them.

Temporary Lumbar Drain as Treatment for Pediatric Fulminant Idiopathic Intracranial Hypertension.

Fulminant idiopathic intracranial hypertension (FIIH) is a subtype of idiopathic intracranial hypertension (IIH) characterized by rapid, severe, progressive vision loss. Surgical intervention is often performed either as a cerebrospinal fluid (CSF) shunt procedure or an optic nerve sheath fenestration or, at times, both. These surgical procedures carry a significant risk of morbidity and failure. We present 2 patients in whom a temporary lumbar drain was successfully used in the management of medically undertreated pediatric FIIH, and circumvented the need for surgical intervention.

Assessment of the American Board of Ophthalmology's Maintenance of Certification Part 4 (Improvement in Medical Practice).

IMPORTANCE: There is disagreement as to whether Maintenance of Certification is creating value for physicians and their patients. To our knowledge, this report provides the first measures of the effectiveness of Part 4 of this activity in assisting ophthalmologists with quality improvement in their practices. OBJECTIVE: To evaluate the effectiveness of the American Board of Ophthalmology's quality improvement program-Maintenance of Certification Part 4 (Improvement in Medical Practice)-in assisting its diplomates with quality improvement in their practices. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis was conducted of the performance of 1046 American Board of Ophthalmology diplomates on Practice Improvement Modules between September 1, 2012, and December 31, 2014. The mean baseline scores for each process or outcome measure on a medical record abstraction were calculated before and after the practice improvement activity. Paired t tests were used to assess improvement before and after the activity. Diplomates' comments and ratings of the usefulness of the activity in assisting them with quality improvement were also analyzed. MAIN OUTCOME MEASURES: Diplomate performance on process and outcome measures before and after a performance improvement activity and diplomate satisfaction that the activity met the stated goals of assistance with quality improvement in their practices. RESULTS: The 1046 American Board of Ophthalmology diplomates completed 1408 Practice Improvement Modules. When measures with participation by at least 20 diplomates were analyzed, there was improvement in 24 of 30 individual process measures (80.0%; 95% CI, 61.4%-92.3%) and in 7 of 18 individual outcome measures (38.9%; 95% CI, 17.3%-64.3%) chosen for improvement by diplomates. Analysis of the mean results for each diplomate on process measures chosen for improvement showed gains occurring in 9 of 12 modules and, for outcomes chosen for improvement, in 6 of 12 modules with at least 20 participants. A total of 826 of 1115 modules (74.1%) assessed by diplomates were rated from good to excellent; positive comments outnumbered negative ones by a ratio of 5:1. CONCLUSIONS AND RELEVANCE: Quantitative and qualitative analyses, while limited by self-report that has not been validated, suggest that the American Board of Ophthalmology's Maintenance of Certification Part 4 can help diplomates improve quality on process, and to a lesser extent, outcome measures. Findings of this study may provide a basis to improve this activity.

Twenty-five years of professional liability in pediatric ophthalmology and strabismus: the OMIC experience.

PURPOSE: To summarize the claims statistics of the Ophthalmic Mutual Insurance Company (OMIC) in the field of pediatric ophthalmology and strabismus (POS). METHODS: Internal OMIC case summaries and defense counsel case evaluations of all claims in the field of POS closed between December 1, 1988, and February 19, 2013 were retrospectively analyzed. RESULTS: A total of 140 claims were closed over the 25-year study period, of which 44 were closed with an indemnity payment. Claims related to strabismus and retinopathy of prematurity (ROP) were most common, and claims related to ROP resulted in the highest indemnity and expense payments. Issues related to follow-up represented the most significant risk factor among system-related claims. CONCLUSIONS: Claims in pediatric ophthalmology and strabismus were infrequent but associated with three times higher average indemnity payments relative to all claims paid by OMIC during the course of the study.

Metastatic tumor to the extraocular muscles: report of 5 cases.

We report the findings in 5 patients with metastases to the extraocular muscles. Familiarity with this condition will aid ophthalmologists in differentiating it from thyroid ophthalmopathy, the most common form of muscle enlargement. Palliative treatment is effective in ameliorating visual symptoms.

N-Salicylideneamino acidato complexes of oxovanadium(IV). The cysteine and penicillamine complexes.

Oxovanadium(IV) complexes with ligands derived from the reaction of salicylaldehyde with L-cysteine and with D- and D,L-penicillamine are prepared. The compounds are characterised by elemental analysis, spectroscopy (UV-VIS, CD, EPR), TG, DSC and magnetic susceptibility measurements (9-295 K). We discuss several aspects related to the structure of these complexes in the solid state and in solution; in particular, the possibility of forming thiazolidine complexes, and their comparison with the characterised complexes is studied by molecular mechanics and density functional theory calculations. The solution structures depend on pH and solvent, and while with L-Cys the spectroscopic results show trends similar to those of the L-Ala and L-Ser systems up to ca. pH 8-9, where thiolate coordination starts being detected, the penicillamine system is quite distinct, namely thiolate coordination occurs for pH > 6.5. In the presence of salicylaldehyde and V(IV)O the desulfydration of cysteine proceeds rapidly, but no similar reaction occurs with penicillamine, although its decomposition is also activated. The DFT calculations do not indicate any energetic basis for this distinct reactivity, which possibly results from different complexes present in the Cys and Pen systems. In the cysteine system, the N-salicylidenedehydroalanine-V(IV)O complex V is believed to form in an intermediate stage of the desulfydration. Further, addition of several nucleophiles to the cysteine reaction mixtures produce amino acid derivatives by a Michael-type base-catalysed addition, a result compatible with the formation of V. The products of these reactions were analysed by TLC and HPLC, and in some cases isolated.