Rony Gelman

Clinical predictors of sustained intraocular pressure elevation due to intravitreal anti-vascular endothelial growth factor therapy.

Purpose: We assess for frequency and predictive factors related to sustained intraocular pressure (IOP) elevation in eyes with neovascular age-related macular degeneration receiving intravitreal injections of ranibizumab and/or bevacizumab. Methods: A total of 328 patients with neovascular age-related macular degeneration (449 eyes) who presented to a single physician over a 6-month period were retrospectively assessed for baseline demographic/clinical information, total number of bevacizumab and/or ranibizumab injections, and sustained IOP elevation on 2 or more consecutive visits (absolute IOP >25 mmHg, increase above baseline >10 mmHg, or IOP of >21 mmHg and increase of >5 mmHg). Cox regression survival analysis and multivariate logistic regression were performed to assess the influence of intravitreal injections on experiencing sustained IOP elevation. Results: Overall, 32 eyes (7.1%) experienced sustained IOP elevation. Survival analysis showed a significant effect of the number of anti–vascular endothelial growth factor injections on sustained IOP elevation (hazard ratio, 1.085; 95% confidence interval: 1.06–1.11, P < 0.001). Also, there was an increased odds ratio (16.1, P = 0.008) of sustained IOP elevation in eyes receiving ≥29 injections compared with ⩽12 injections. After controlling for the confounder (prior intravitreal steroid injection), total number of injections still showed a statistically significant association (P = 0.002). Conclusion: A greater number of intravitreal anti–vascular endothelial growth factor injections is associated with an increased risk for sustained IOP elevation in eyes with neovascular age-related macular degeneration receiving intravitreal ranbizumab and/or bevacizumab.

FUNDUS AUTOFLUORESCENCE IMAGING IN A PATIENT WITH RAPIDLY DEVELOPING SCOTOMA

PURPOSE To evaluate the findings in a case of acute macular neuroretinopathy involving sudden development of scotomas accompanied by rapid focal increases in fundus autofluorescence. METHODS The clinical presentation of the patient was documented by color fundus photographs, fundus autofluorescence, infrared imaging, and high-resolution spectral domain optical coherence tomography. The scotomas were assessed by Humphrey visual field 10-2 and MP-1 microperimetry. RESULTS Visual field defects exhibited spatial correspondence with wedge-shaped lesions demonstrable in color fundus photographs and infrared imaging. It was notable that the lesions exhibited increased intensity on autofluorescence images obtained within 3 weeks of presentation. Optical coherence tomography revealed focal loss of photoreceptor inner segment/outer segment junctions in both eyes. CONCLUSION This case was distinguished by the relative rapidity with which the lesions became hyperautofluorescent in fundus autofluorescence images. Given that the bisretinoids that are the source of autofluorescence form in photoreceptor cells and are transferred to retinal pigment epithelium secondarily, the rapid increase in autofluorescence is unlikely to only reflect retinal pigment epithelium status and is more likely to be indicative of photoreceptor cell dysfunctioning and loss of structural integrity.

Plus disease in retinopathy of prematurity: Diagnostic impact of field of view

Purpose: To examine the impact of retinal field of view and magnification on interexpert reliability of plus disease diagnosis in retinopathy of prematurity. Methods: Fifteen wide-angle images from infants with retinopathy of prematurity were cropped and adjusted in magnification to create 2 additional image categories: medium angle (40°–50°) and narrow angle (20°–30°). These 45 images were uploaded to a Web-based system and interpreted independently by 13 experts of retinopathy of prematurity using a 3-level (plus, preplus, neither) and 2-level (plus, not plus) classification. Absolute agreement and kappa statistics were calculated to compare interexpert reliability. Results: In the 3-level classification, ≥70% experts agreed on the same diagnosis in 8 of the 15 wide-angle images (53%), but only in 3 of the 15 medium-angle (20%) and 3 of the 15 narrow-angle (20%) images. In the 2-level classification, ≥80% experts agreed on the same diagnosis in 11 of the 15 wide-angle images (73%), but only in 9 of the 15 medium-angle (60%) and 3 of the 15 narrow-angle (20%) images. Mean kappa of each expert compared with all other experts was 0.40 to 0.59 in 8 of 13 experts (62%) using wide-angle images, was 0 to 0.19 in 7 of 13 experts (54%) using medium-angle images, and was 0.20 to 0.39 in 9 of 13 experts (69%) using narrow-angle images. Conclusion: Interexpert agreement in plus disease diagnosis in wide-angle images is higher than from medium-angle and narrow-angle images. Plus disease is defined using a narrow-angle standard published photograph, yet this study suggests that peripheral findings also contribute to diagnosis.

Linking biomedical language information and knowledge resources: GO and UMLS.

Integration of various informatics terminologies will be an essential activity towards supporting the advancement of both the biomedical and clinical sciences. The GO consortium has developed an impressive collection of biomedical terms specific to genes and proteins in a variety of organisms. The UMLS is a composite collection of various medical terminologies, pioneered by the National Library of Medicine. In the present study, we examine a variety of techniques for mapping terms from one terminology (GO) to another (UMLS), and describe their respective performances for a small, curated data set attained from the National Cancer Institute, which had precision values ranging from 30% (100% recall) to 95% (74% recall). Based on each techniques performance, we comment on how each can be used to enrich an existing terminology (UMLS) in future studies and how linking biological terminologies to UMLS differs from linking medical terminologies.

An evaluation of hybrid methods for matching biomedical terminologies: Mapping the gene ontology to the UMLS®

Integration of disparate biomedical terminologies is becoming increasingly important as links between biological science and clinical medicine grow. Mapping concepts in the Gene Ontology (GO) to the UMLS may help further this integration and allow for more efficient information exchange among researchers. Using a gold standard of GO term--UMLS concept mappings provided by the NCI, we examined the performance of various published and combined mapping techniques, in order to maximize precision and recall. We found that for the previously published techniques precision varied between (0.61-0.95), and recall varied from (0.65-0.90), whereas for the hybrid techniques, precision varied between (0.66-0.97), and recall from (0.59-0.93). Our study reveals the benefits of using mapping techniques that incorporate domain knowledge, and provides a basis for future approaches to mapping between distinct biomedical vocabularies.

Plus Disease in Retinopathy of Prematurity: Quantitative Analysis of Standard Published Photograph

dose group. At the visit 10±2 weeks after stopping the levodopa treatment, the mean change in visual acuity in the amblyopic eye from baseline was 5 (±4) letters in the lowerdose group and 4 (±5) letters in the higher-dose group. Levodopa-carbidopa was not discontinued by any subject during the 9-week dosing regimen. Adverse events were reported for 8 of 16 subjects (29 events) in the lowerdose group and 11 of 17 subjects (26 events) in the higherdose group (eTable 2). No adverse events were considered serious. Headaches were reported by 6 subjects; a cold, upper respiratory tract infection, and cough were reported by 6; rash was reported by 4; and nausea and vomiting were reported by 3.

Juvenile-Onset Macular Degeneration and Allied Disorders

While age-related macular degeneration (AMD) is a leading cause of central vision loss among the elderly, many inherited diseases that present earlier in life share features of AMD. These diseases of juvenile-onset macular degeneration include Stargardt disease, Best disease, retinitis pigmentosa, X-linked retinoschisis, and other allied disorders. In particular, they can be accompanied by the appearance of drusen, geographic atrophy, macular hyperpigmentation, choroidal neovascularization, and disciform scarring just as in AMD, and often may be confused for the adult form of the disease. Diagnosis based on funduscopic findings alone can be challenging. However, the use of diagnostic studies such as electroretinography, electrooculography, optical coherence tomography, and fundus autofluorescence in conjunction with genetic testing can lead to an accurate diagnosis.

Evaluation of Vascular Disease Progression in Retinopathy of Prematurity Using Static and Dynamic Retinal Images

PURPOSE To measure accuracy and speed for detection of vascular progression in retinopathy of prematurity (ROP) from serial images. Two strategies are compared: static side-by-side presentation and dynamic flickering of superimposed image pairs. DESIGN Prospective comparative study. METHODS Fifteen de-identified, wide-angle retinal image pairs were taken from infants who eventually developed plus disease. Image pairs representing vascular disease progression were taken ≥1 week apart, and control images without progression were taken on the same day. Dynamic flickering pairs were created by digital image registration. Ten experts independently reviewed each image pair on a secure website using both strategies, and were asked to identify progression or state that images were identical. Accuracy and speed were measured, using examination date and ophthalmoscopic findings as a reference standard. RESULTS Using static images, experts were accurate in a mean (%) ± standard deviation (SD) of 11.4 of 15 (76%) ± 1.7 image pairs. Using dynamic flickering images, experts were accurate in a mean (%) ± SD of 11.3 of 15 (75%) ± 1.7 image pairs. There was no significant difference in accuracy between these strategies (P = .420). Diagnostic speed was faster using dynamic flickering (24.7 ± 8.3 seconds) vs static side-by-side images (40.3 ± 18.3 seconds) (P = .002). Experts reported higher confidence when interpreting dynamic flickering images (P = .001). CONCLUSIONS Retinal imaging provides objective documentation of vascular appearance, with potentially improved ability to recognize ROP progression compared to standard ophthalmoscopy. Speed of identifying vascular progression was faster by review of dynamic flickering image pairs than by static side-by-side images, although there was no difference in accuracy.

Multimodal imaging in a case of deferoxamine-induced maculopathy.

PURPOSE To report a case of deferoxamine-induced maculopathy and present the use of multimodal retinal imaging to study this disease entity. METHODS This is an observational case report of one patient. Multimodal imaging with fundus autofluorescence, infrared imaging, and spectral domain optical coherence tomography was used to investigate the macular changes induced by deferoxamine toxicity. RESULTS A 53-year-old man with history of β-thalassemia presented with decreased vision in both eyes 1 month after initiating deferoxamine therapy. Infrared imaging showed areas of increased stippled infrared intensity through the macula. Fundus autofluorescence revealed diffuse areas of stippled hyperautofluorescence and hypoautofluorescence. Spectral domain optical coherence tomography changes included disruption of the ellipsoid zone, attenuation of the photoreceptors, and deposits within the retinal pigment epithelium. CONCLUSION A case of deferoxamine-induced maculopathy was described and the use of multimodal retinal imaging to study this disease entity was presented.

Hyperautofluorescent macular ring in a series of patients with enhanced S-cone syndrome.

The authors describe fundus autofluorescence (AF) and spectral-domain optical coherence tomography (SD-OCT) findings in three patients with enhanced S-cone syndrome and their correlation around the hyperautofluorescent ring border. Patients had AF imaging in combination with SD-OCT line-scans through the fovea, at the posterior pole, and at a temporal locus centered on the ring border. All eyes demonstrated a macular ring of high-intensity AF. The inner segment ellipsoid band showed thinning and disorganization toward the ring border, where it was lost.