DataMed - an open source discovery index for finding biomedical datasets.

OBJECTIVE: Finding relevant datasets is important for promoting data reuse in the biomedical domain, but it is challenging given the volume and complexity of biomedical data. Here we describe the development of an open source biomedical data discovery system called DataMed, with the goal of promoting the building of additional data indexes in the biomedical domain. MATERIALS AND METHODS: DataMed, which can efficiently index and search diverse types of biomedical datasets across repositories, is developed through the National Institutes of Health-funded biomedical and healthCAre Data Discovery Index Ecosystem (bioCADDIE) consortium. It consists of 2 main components: (1) a data ingestion pipeline that collects and transforms original metadata information to a unified metadata model, called DatA Tag Suite (DATS), and (2) a search engine that finds relevant datasets based on user-entered queries. In addition to describing its architecture and techniques, we evaluated individual components within DataMed, including the accuracy of the ingestion pipeline, the prevalence of the DATS model across repositories, and the overall performance of the dataset retrieval engine. RESULTS AND CONCLUSION: Our manual review shows that the ingestion pipeline could achieve an accuracy of 90% and core elements of DATS had varied frequency across repositories. On a manually curated benchmark dataset, the DataMed search engine achieved an inferred average precision of 0.2033 and a precision at 10 (P@10, the number of relevant results in the top 10 search results) of 0.6022, by implementing advanced natural language processing and terminology services. Currently, we have made the DataMed system publically available as an open source package for the biomedical community.

Multimodal imaging in handheld laser-induced maculopathy.

PURPOSE: To describe the clinical and imaging findings in 3 patients with maculopathy secondary to handheld laser exposure. DESIGN: Retrospective, observational case series. METHODS: We evaluated the multimodal imaging including fundus autofluorescence and spectral-domain optical coherence tomography (OCT) for 3 patients with histories of exposure to handheld lasers. RESULTS: An 18-year-old woman with a history of repetitive self-inflicted handheld laser exposure was found to have bilateral outer retinal streaks in the macula and the superior peripheral retina on both ophthalmoscopy and multimodal imaging. Initial spectral-domain OCT revealed vertical hyper-reflective bands at the level of the outer retina corresponding to the streaks. An 11-year-old boy who played with a green laser developed a yellow foveal lesion and outer retinal streaks in the superior macula. Spectral-domain OCT showed vertical hyper-reflective bands in the outer retina corresponding to the streaks. A 14-year-old boy developed bilateral focal foveal lesions and ellipsoid loss on spectral-domain OCT following peer-inflicted laser injury. CONCLUSIONS: In a series of 3 patients, outer retinal streaks were associated with self-inflicted handheld laser injury. In contrast, accidental and peer-inflicted laser injuries were found to result in focal foveal lesions.

Diffuse retinal capillary leakage in coats disease.

PURPOSE: Coats disease is a rare condition characterized by retinal vascular telangiectasia, aneurysms, and leakage from these abnormal blood vessels. We report the phenomenon and treatment of Coats disease with diffuse hyperpermeability from angiographically normal retinal capillaries. METHODS: This case series describes two patients with Coats disease, diagnosed based on fundus photography and fluorescein angiography. The first patient was treated with intravitreal bevacizumab and limited laser photocoagulation. The second patient was treated only with limited photocoagulation. RESULTS: The diffuse exudation from normal retinal capillaries resolved with treatment of the focal primary vascular Coats lesions. CONCLUSION: Vasculopathies such as Coats disease may produce diffuse hyperpermeability of otherwise normal capillaries in the fundus. Limiting treatment only to the primary Coats lesions is a minimally invasive strategy that preserves normal capillaries.

The expanded spectrum of focal choroidal excavation.

OBJECTIVE: To describe the clinical and imaging findings in patients with focal choroidal excavation. METHODS: Retrospective observational case series. The medical records of 12 patients (13 eyes) with focal choroidal excavation were reviewed. Clinical histories and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and enhanced depth imaging spectral-domain optical coherence tomography) were analyzed. RESULTS: The mean age of the patients was 45 years (range, 22-62 years). Four patients were Asian. Mean visual acuity was 20/31 (range, 20/20 to 20/100). Mean refractive error was -3.54 diopters (D) (range, 6.00 to -8.00 D). One patient had bilateral involvement. All patients manifested varying degrees of foveal pigmentary changes that were usually hypoautofluorescent on fundus autofluorescence images. Fluorescein angiographic findings varied with degree of retinal pigment epithelial alterations. Indocyanine green angiography revealed relative hypofluorescence. In 7 eyes, spectral-domain optical coherence tomography revealed outer retinal layers conforming to retinal pigment epithelial alterations within the excavation. In the other 6 eyes, spectral-domain optical coherence tomography revealed a separation between the outer retina and the retinal pigment epithelium within the excavation. In 7 eyes studied with enhanced depth imaging spectral-domain optical coherence tomography, there was no evidence of scleral ectasia. Mean choroidal thickness of the uninvolved choroid was thicker than normal at 319 µm (range, 244-439 µm). All lesions remained stable except for in 1 eye, which had findings of central serous chorioretinopathy and secondary type 2 (subretinal) neovascularization. CONCLUSION: Focal choroidal excavation is a newly described idiopathic entity in eyes having 1 or more focal areas of choroidal excavation. In some patients, there may be an association with central serous chorioretinopathy. Although most lesions remain stable, secondary choroidal neovascularization may occur.

Hemorrhagic recurrence of neovascular age-related macular degeneration not predicted by spectral domain optical coherence tomography.

PURPOSE: To report a case in which a patient with neovascular age-related macular degeneration developed a large submacular hemorrhage 2 days after spectral domain optical coherence tomography imaging, which revealed no intra- or subretinal fluid. METHODS: A noninterventional case report. RESULTS: A 93-year-old woman with neovascular age-related macular degeneration was seen for a regular follow-up examination 3 years after treatment with verteporfin photodynamic therapy in which lesion quiescence was achieved. Visual acuity was stable at 20/200, and spectral domain optical coherence tomography scans using 2 different instruments revealed no intra- or subretinal fluid. Two days after clinical examination and imaging, the patient presented with a large submacular hemorrhage and 5/400 vision. CONCLUSION: Hemorrhagic exudation from choroidal neovascularization in age-related macular degeneration may occur suddenly, even in the absence of fluid detected by spectral domain optical coherence tomography.

Disappearance of drusen after rhegmatogenous retinal detachment.

PURPOSE: To describe the disappearance of drusen after rhegmatogenous retinal detachment. METHODS: Descriptive case report. RESULTS: A 72-year-old man with confluent subfoveal drusen developed a rhegmatogenous retinal detachment and subsequently improved in vision with disappearance of the subfoveal drusen less than 1 month after repair. CONCLUSION: Rhegmatogenous retinal detachment can result in the disappearance of drusen.

Outer retinal tubulation: a novel optical coherence tomography finding.

OBJECTIVE: To describe tubular structures found in the outer retina seen in a variety of retinal disorders. METHODS: Sixty-nine eyes of 63 patients were examined with spectral-domain optical coherence tomography. Optical coherence tomography C-scans were correlated with their corresponding B-scans. The prevalence, number, size, and shape of the tubular structures were determined. RESULTS: Branching tubules were identified in the outer retina of 54 patients with age-related macular degeneration and in 9 patients with other diagnoses. The tubules appeared as round or ovoid hyporeflective spaces with hyperreflective borders on the B-scans, measuring 40 to 140 microm high and 40 to 2260 microm wide. Morphologic features ranged from single straight or branching tubules to complex cavitary networks, usually overlying areas of pigment epithelial alteration or subretinal fibrosis. The tubules generally remained stable over time. In a retinal practice specializing in advanced age-related macular degeneration, these structures were identified in 60 of 248 patients (24.2%) seen during a 3-month period. CONCLUSIONS: Degenerating photoreceptors may become arranged in a circular or ovoid fashion during a process we propose to term outer retinal tubulation. These changes are apparently common in advanced diseases affecting the outer retina and retinal pigment epithelium. This observation has practical implications because these findings can be misinterpreted as intraretinal or subretinal fluid, possibly prompting unnecessary interventions.

Enhanced depth imaging optical coherence tomography of the choroid in central serous chorioretinopathy.

PURPOSE: The purpose of the study was to evaluate the choroidal thickness in patients with central serous chorioretinopathy, a disease attributed to increased choroidal vascular hyperpermeability. METHODS: Patients with central serous chorioretinopathy underwent enhanced depth imaging spectral-domain optical coherence tomography, which was obtained by positioning a spectral-domain optical coherence tomography device close enough to the eye to acquire an inverted image. Seven sections, each comprising 100 averaged scans, were obtained within a 5 degrees x 30 degrees rectangle to encompass the macula. The subfoveal choroidal thickness was measured from the outer border of the retinal pigment epithelium to the inner scleral border. RESULTS: The mean age of subjects undergoing enhanced depth imaging spectral-domain optical coherence tomography was 59.3 years (standard deviation, 15.8 years). Seventeen of 19 patients (89.5%) were men, and 12 (63.2%) patients had bilateral clinical disease. The choroidal thickness measured in 28 eligible eyes of the 19 patients was 505 microm (standard deviation, 124 microm), which was significantly greater than the choroidal thickness in normal eyes (P < or = 0.001). CONCLUSION: Enhanced depth imaging spectral-domain optical coherence tomography demonstrated a very thick choroid in patients with central serous chorioretinopathy. This finding provides additional evidence that central serous chorioretinopathy may be caused by increased hydrostatic pressure in the choroid.

Enhanced depth imaging optical coherence tomography of the choroid in highly myopic eyes.

PURPOSE: To measure macular choroidal thickness (CT) in highly myopic eyes using enhanced depth imaging optical coherence tomography (OCT). DESIGN: Retrospective, observational case series. METHODS: Enhanced depth imaging OCT images were obtained in highly myopic eyes (> or =6 diopters [D]). Images of CT were obtained by positioning a spectral-domain OCT device close enough to the eye to acquire an inverted image. CT was measured from the outer border of the retinal pigment epithelium to the inner scleral border at 1000-mum intervals of a horizontal section from 3 mm temporal to the fovea to 3 mm nasal to the fovea. Statistical analysis was performed to evaluate CT at each location and to correlate CT with age and refractive error. RESULTS: The mean age of the 31 patients (55 eyes) was 59.7 years (+/- 17.6 years; range, 24 to 90 years), and the mean refractive error was -11.9 D (+/- 3.7 D). The mean subfoveal CT was 93.2 microm (+/- 62.5 microm) and was correlated negatively with age (P = .006), refractive error (P < .001), and history of choroidal neovascularization (P = .013). Regression analysis suggested that subfoveal CT decreased by 12.7 mum for each decade of life and by 8.7 microm for each D of myopia. CONCLUSIONS: The choroid in highly myopic eyes is very thin and undergoes further thinning with increasing age and degree of myopia. Abnormalities of the choroid may play a role in the pathogenesis of myopic degeneration.

A pilot study of enhanced depth imaging optical coherence tomography of the choroid in normal eyes.

PURPOSE: To measure macular choroidal thickness in normal eyes at different points using enhanced depth imaging (EDI) optical coherence tomography (OCT) and to evaluate the association of choroidal thickness and age. DESIGN: Retrospective, observational case series. METHODS: EDI OCT images were obtained in patients without significant retinal or choroidal pathologic features. The images were obtained by positioning a spectral-domain OCT device close enough to the eye to acquire an inverted image. Seven sections were obtained within a 5 x 30-degree area centered at the fovea, with 100 scans averaged for each section. The choroid was measured from the outer border of the retinal pigment epithelium to the inner scleral border at 500-microm intervals of a horizontal section from 3 mm temporal to the fovea to 3 mm nasal to the fovea. Statistical analysis was performed to evaluate variations of choroidal thickness at each location and to correlate choroidal thickness and patient age. RESULTS: The mean age of the 30 patients (54 eyes) was 50.4 years (range, 19 to 85 years), and 14 patients (46.7%) were female. The choroid was thickest underneath the fovea (mean, 287 microm; standard deviation, +/- 76 microm). Choroidal thickness decreased rapidly in the nasal direction and averaged 145 microm (+/- 57 microm) at 3 mm nasal to the fovea. Increasing age was correlated significantly with decreasing choroidal thickness at all points measured. Regression analysis suggested that the subfoveal choroidal thickness decreased by 15.6 microm for each decade of life. CONCLUSIONS: Choroidal thickness seems to vary topographically within the posterior pole. The thickness of the choroid showed a negative correlation with age. The decrease in the thickness of the choroid may play a role in the pathophysiologic features of various age-related ocular conditions.

Diagnostic vitrectomy for the diagnosis and management of posterior uveitis of unknown etiology.

PURPOSE OF REVIEW: Diagnostic vitrectomy is performed in cases of posterior segment inflammation that are suspicious for malignancy or infection and require tissue confirmation. Advances in vitrectomy technique and laboratory tests have improved the diagnostic yield in these challenging cases. The methods for obtaining vitreous specimens and the diagnostic tests used to analyze them are discussed. RECENT FINDINGS: Ancillary tests have been invaluable in addressing the diagnostic limitations of traditional histopathologic and microbiologic analyses. Flow cytometry, gene rearrangement studies, and cytokine measurements are useful adjuncts to cytology for the diagnosis of malignancy, in particular primary intraocular lymphoma. Microbial DNA amplification by polymerase chain reaction and intraocular antibody measurement has been shown to detect the presence of infection by organisms that are difficult to culture. SUMMARY: When performed appropriately, diagnostic vitrectomy with carefully selected ancillary testing can lead to a definitive diagnosis in a large proportion of cases.

Intravitreal triamcinolone as adjunctive treatment to laser panretinal photocoagulation for concomitant proliferative diabetic retinopathy and clinically significant macular oedema.

PURPOSE: To evaluate the effect of intravitreal injections of triamcinolone acetonide (IVTA) combined with panretinal photocoagulation (PRP) on visual acuity (VA) and foveal thickness in patients with concomitant high-risk proliferative diabetic retinopathy (PDR) and clinically significant macular oedema (CSMO). METHODS: This retrospective interventional case series included seven eyes diagnosed with both high-risk PDR and CSMO that underwent PRP and a single injection of 4 mg of IVTA. The main outcome measures were VA and foveal thickness, measured by optical coherence tomography (OCT) before treatment and throughout the follow-up period. RESULTS: Median follow-up was 301 days (range 180-715 days). Foveal thickness data were available for four of seven eyes. Before the combined treatment, median LogMAR (logarithm of the minimum angle of resolution) VA and median foveal thickness were 1 (Snellen 20/200, range 20/40-20/800) and 559 microm (range 333-689 microm), respectively. After treatment, median vision improved to LogMAR 0.544 (Snellen 20/70, range 20/40-20/1000) (P = 0.13). Vision improved or remained stable in six of seven eyes. Median foveal thickness at final follow-up was 436 microm (range 259-623 microm) (P = 0.15). Foveal thickness decreased or remained stable in all eyes. CONCLUSION: The addition of IVTA to PRP in the treatment of eyes with high-risk PDR and CSMO may prevent PRP-induced foveal thickening and loss of vision.

Sarcoidosis.

PURPOSE OF REVIEW: Research conducted in recent years has added to our current understanding of the epidemiologic, immune, and genetic factors involved in the pathogenesis of sarcoidosis. RECENT FINDINGS: Exposure to an environmental or occupational antigen in a genetically susceptible individual is thought to trigger an immunologic response. The cells and cytokines that lead to granuloma formation have been an area of active study. Certain human leukocyte antigen genes appear to play roles in susceptibility and disease phenotype, and two genome scans have identified candidate genes. A genetic susceptibility has been suggested for ocular involvement as well. High-resolution computed tomography has been invaluable in selected patients, and new radionucleotide techniques are currently being developed. The tumor necrosis factor alpha antagonist infliximab has been used successfully in cases of refractory sarcoidosis, whereas the use of etanercept in the treatment of sarcoidosis has been disappointing, and may actually cause the disease. SUMMARY: Recent advances in our understanding of the immunologic events in sarcoidosis may lead to developments in treatments that would further decrease systemic and ocular morbidity.

Adverse events after intravitreal triamcinolone in patients with and without uveitis.

PURPOSE: To evaluate the rates of adverse ocular events after intravitreal triamcinolone acetonide (IVTA) injection in patients with and without uveitis. DESIGN: Retrospective observational case series. PARTICIPANTS: Two hundred twenty-two eyes of 173 patients were included in the study: 45 eyes of 31 patients with macular edema (ME) due to uveitis and 177 eyes of 142 patients with ME secondary to other etiologies. METHODS: Retrospective review of patients who received IVTA at the Cole Eye Institute for ME attributable to various causes between the years 2001 and 2005. Data review of clinical records included patient demographics, etiology of ME, and adverse outcomes after injection. Rates of adverse outcomes in patients with and without uveitis were compared. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) elevation and posterior subcapsular cataract (PSC) progression. RESULTS: Uveitis patients were significantly younger, more likely to be female, and more likely to have had prior posterior sub-Tenon's capsule steroid injection and/or glaucoma therapy than their nonuveitis counterparts. In a multivariate analysis adjusting for the differences in these factors, the presence of uveitis was the strongest risk factor for an adverse IOP event (odds ratio, 2.5; 95% confidence interval [CI], 1.0-6.1; P = 0.05). The odds of having a documented increase in PSC after IVTA injection were 5.6 times greater in uveitis eyes (P = 0.007; 95% CI, 1.6-19.6). CONCLUSIONS: Intraocular pressure elevation and PSC progression occurred with greater frequency in uveitis patients receiving IVTA. Patients with uveitis treated with IVTA should be counseled about these risks and monitored closely.

Role of rigid gas-permeable scleral contact lenses in the management of advanced atopic keratoconjunctivitis.

PURPOSE: To describe the use of rigid gas-permeable scleral contact lenses (ScCL) in the treatment and visual rehabilitation of patients with medically controlled advanced atopic keratoconjunctivitis (AKC). METHODS: Retrospective chart review of 10 eyes with medically controlled advanced AKC whose treatment included the use of ScCL for protection of the cornea from the ocular surface environment and visual rehabilitation. Outcomes measured were changes in biomicroscopic findings and visual acuity. RESULTS: Median follow-up period after ScCL fitting was 20.5 months (range, 14-32 months). An improvement in conjunctival hyperemia and corneal epithelial defects was observed in all eyes. Median best-corrected visual acuity before ScCL was logMAR 0.651 (Snellen 20/90; range, 20/45-20/400). After proper ScCL fitting, median logMAR visual acuity was 0.239 (Snellen 20/35; range, 20/20-20/50; P = 0.001). All patients gained at least 1 line of vision after initiation of ScCL, and 9 of 10 eyes experienced an improvement of at least 2 lines of vision. ScCL use was well tolerated by all patients, and no complications or infections occurred as a result of ScCL wear. CONCLUSIONS: Rigid gas-permeable ScCL are useful and safe to use in the management of the ocular surface and in the visual rehabilitation of eyes with medically controlled advanced AKC.

Intravitreal bevacizumab for macular edema due to occlusive vasculitis.

Systemic vasculitides can cause retinal vascular pathology, including cotton-wool spots, retinal hemorrhages, vascular occlusion, and capillary nonperfusion. Two main causes of visual decline include macular edema and retinal neovascularization. Presumably, both of these complications are caused by increased intraocular levels of vascular growth and permeability factors. We report a patient with occlusive retinal vasculitis associated with mixed connective tissue disease who was treated with intravitreal bevacizumab for chronic macular edema. One month after treatment, visual acuity improved from 20/80 to 20/60, and foveal thickness decreased from 543 microns to 306 microns. This effect persisted for at least 3 months after treatment. No complications, including increased retinal ischemia, were observed.

Conjunctival involvement in Churg-Strauss syndrome.

PURPOSE: To describe an unusual case of Churg-Strauss syndrome (CSS) that presented with a conjunctival nodule and was successfully treated with oral corticosteroids. METHODS: Case report. RESULTS: A 30-year-old woman with a history of adult-onset asthma, seasonal allergies, and a lung mass presented with a nodular elevation of the conjunctiva. Excisional biopsy demonstrated necrotizing eosinophilic granulomas. Systemic evaluation revealed peripheral eosinophilia and elevated IgE, consistent with Churg-Strauss syndrome. The patient's symptoms and eosinophilia resolved after an increase in the dose of oral corticosteroids. CONCLUSIONS: This case describes a unique presentation of conjunctival involvement in CSS that differs from prior case reports by having a small, well-demarcated nodule and lacking signs of active inflammation.

Vitrectomy for the diagnosis and management of uveitis of unknown cause.

PURPOSE: To determine the diagnostic yield of tests commonly used for vitreous fluid analysis in eyes with suspected intraocular infection or malignancy. DESIGN: Noncomparative interventional case series. PARTICIPANTS: Forty-four consecutive patients (45 eyes) treated from 1998 through 2006 with posterior segment inflammation who underwent pars plana vitrectomy for diagnostic purposes. INTERVENTION: Vitreous specimens obtained via pars plana vitrectomy were analyzed by microbiologic culture, cytologic analysis, and flow cytometry. MAIN OUTCOME MEASURES: Diagnostic yield and sensitivity of each test performed on vitreous specimens and visual outcomes of eyes that underwent diagnostic vitrectomy (DVx). RESULTS: Preoperative diagnoses were infection in 15 eyes and malignancy in 30 eyes. Overall, vitreous analysis identified a specific cause in 9 (20%) of 45 eyes. The overall sensitivity of DVx was 63.6%. The sensitivities of individual tests were: culture, 50%; cytologic analysis, 66.7%; and flow cytometry, 83.3%. The yields of diagnostic tests were: culture, 5.7%; cytologic analysis, 14.3%; and flow cytometry, 20.6%. Final diagnoses were infection in 6 eyes, malignancy in 9 eyes, and idiopathic in 30 eyes. Mean visual acuity improved significantly in the first 6 months after DVx. Visual acuity improved in 60% of eyes, with 37.8% of eyes improving by 3 lines or more. CONCLUSIONS: Analysis of vitreous fluid by widely available tests is useful in identifying intraocular infection or malignancy. Most patients experienced a substantial improvement in vision.

Multifocal posterior necrotizing retinitis.

PURPOSE: To describe the clinical features of an acute, inflammatory, and progressive retinal necrosis that affects primarily the posterior pole. DESIGN: Retrospective, interventional case series. METHODS: Twenty-seven eyes of 24 patients diagnosed with and treated for acute retinal necrosis (ARN) were categorized into two groups according to the predominant location of retinitis at presentation: either in the peripheral retina or in the posterior pole. Clinical features, disease progression, visual outcomes, and complications of these two groups were compared. RESULTS: Fifteen eyes demonstrated the known peripheral retinitis pattern, and 12 eyes exhibited a pattern of retinitis that affected mainly the posterior pole. Eyes with peripheral retinitis showed focal, well-demarcated areas of retinal necrosis in the periphery with rapid circumferential progression and rare involvement of the posterior pole. All eyes with posterior pole retinitis had multifocal deep lesions posterior to the vortex veins at presentation, and half of these eyes had lesions in the macula. These lesions progressed to patches of confluent retinitis in both the periphery and the posterior pole. There was no significant difference between the two groups in the incidence of anterior chamber and vitreous cells, vascular sheathing, retinal hemorrhages, or optic disk edema. Patients with posterior retinitis involvement seemed to have a worse visual outcome during the first two years after diagnosis. The Cox proportional hazards model suggested a higher incidence of retinal detachment in patients with posterior retinitis (P = .07). CONCLUSIONS: The authors report a pattern of herpetic retinitis that affects predominantly the posterior pole and may have a worse visual prognosis and a higher rate of retinal detachment.