How Lingering Fusional Adaptation Influences the Bielschowsky Head Tilt Test in Superior Oblique Paresis.

BACKGROUND: The lack of a positive Bielschowsky head tilt test (BHTT) is commonly seen as an indicator that superior oblique paresis (SOP) is not present. This study investigated the influence of fusion on the BHTT in unilateral SOP. PATIENTS/METHODS AND MATERIAL: We analyzed vertical fusional vergence using our eye-tracking haploscope and the value of BHTT difference (BHTTD) in 11 patients who were diagnosed with congenital unilateral SOP and able to fuse. RESULTS: Patients used one of three different mechanisms of vertical vergence to achieve fusion. The three fusional mechanisms were associated with a significantly different BHTTD (p < 0.05). Seven of the eleven patients used vertical recti-mediated fusion and had a mean BHTTD ± SD of 21.7 ± 6.3 prism diopters (PD). Three of these patients whom we measured after a patch test for at least 30 min showed a decreased BHTTD (12.7 ± 3.8 PD). Three of the eleven patients used a mixed (oblique/rectus) fusional mechanism and had a mean BHTTD ± SD of 9.3 ± 8.6 PD. Of these patients, the one whom we measured after patching showed an increase of 11 PD in BHTTD. The remaining patient used oblique muscle-mediated fusion and had a BHTTD of only 3 PD that increased to 21 PD after patching. One explanation for this BHTT behavior in the latter patient involves lingering vergence adaptation of the "paretic" superior oblique muscle (SOM) and contralateral inferior oblique muscle, which makes these muscles more effective when activated, as is the case on ipsilateral head tilt (part of the ocular counter-roll mechanism), lessening the expected increase in hyperdeviation. Similarly, in our patients with mixed fusion, the vergence-adapted "paretic" SOM and contralateral superior rectus muscle are activated on ipsilateral and contralateral tilt, respectively, lessening the hyperdeviation in both directions. In the other seven patients, however, the vergence-adapted ipsilateral inferior rectus muscle and contralateral superior rectus muscle are activated on contralateral tilt, accentuating the BHTTD. CONCLUSION: Depending upon the specific muscles used for vertical fusion, the BHTTD is decreased or increased. The presence of a large BHTTD points to lingering or persisting fusional tonus involving the vertical rectus muscles. The lack of a positive BHTT does not rule out the diagnosis of SOP, but rather may be caused by lingering or persevering fusional tonus involving the oblique muscles. Performing the BHTT after a patch test for a minimum of 30 minutes may be necessary to reveal the BHTTD, supporting the diagnosis of SOP.

Disconjugacy of Eye Movements during Attempted Fixation: A Sufficient Marker for Amblyopia?

BACKGROUND: To investigate whether detection of disconjugacy of eye movements during attempted fixation, or interocular position instability, may serve as a single sensitive test for amblyopia. PATIENTS/METHODS AND MATERIAL: Binocular eye movements were recorded at 500 Hz using the EyeLink 1000 eye tracker (SR Research Ltd., Kanata, Ontario, Canada) and analyzed using EyeLink software and Matlab (MathWorks, Natick, MA, USA). Eight subjects (four amblyopes, one successfully treated amblyope, and three non-amblyopes: 7 - 44 years) were asked to fixate on a stationary cross subtending 0.5° at 57 cm. Interocular position instability was quantified by calculating the minimum area bivariate contour ellipse (BCEA) encompassing 68% of the difference between right and left eye position points during 20-second viewing epochs. For statistical analysis, BCEA values, as well as visual acuity and stereoacuity, were normalized by base-10 logarithm transformation. RESULTS: The amblyopic subjects with persistent vision loss (one anisometropic, two strabismic, one deprivation; uncorrected visual acuity range 20/60 - 20/300, corrected stereoacuity range nil-400 arcsec) showed significantly higher interocular position instability (larger 68% BCEAs) than the non-amblyopic subjects (uncorrected visual acuity range 20/20 - 20/800, corrected stereoacuities of 20 arcsec) and the successfully treated strabismic amblyope (to the 20/20 level of visual acuity and 70 arcsec of stereoacuity) during binocular viewing trials; p < 0.01. Interocular position stability was strongly correlated with stereoacuity (in that better stereoacuity was associated with lower 68% BCEAs; r = 0.95), but not with visual acuity (r = 0.20). CONCLUSION: Interocular position instability appears to differentiate amblyopic from non-amblyopic subjects and appears to improve after successful treatment. Interocular position instability may therefore prove to be a single sensitive test for the presence of amblyopia. As a difference measure, it is inherently less susceptible to head motion and calibration error, as well as to conjugate eye motion, and as such is expected to be somewhat immune to latent nystagmus. Interocular position instability may also be useful to guide treatment, especially in preverbal children, and to assess the efficacy of novel treatments. Further research is required to establish optimal interocular position instability thresholds and to determine how specific this measure is to amblyopia.

Characteristics of morphologic macular abnormalities in neuroimmunology practice.

BACKGROUND: Morphologic macular abnormalities (MMAs) are frequently seen on macular optical coherence tomography (OCT) imaging in neuroimmunology practice, yet studies pragmatically assessing prevalence and risk factors of MMAs to date are limited. OBJECTIVE: To describe the characteristics of MMAs in a neuroimmunology-based academic practice. METHODS: Cross-sectional study of 1450 patients (2900 eyes) who underwent spectral-domain macular OCT between June 2010 and June 2012. The association between MMAs and demographic variables was analyzed using mixed-effects logistic regression. Odds ratios (ORs) were calculated per 5-year age increments. RESULTS: MMAs were observed in 338/2872 eyes (11.7%) of 232/1445 participants (16.1%). The most common abnormalities identified, included drusen (6.0%), epiretinal membrane (ERM; 5.5%), and microcystoid macular pathology (MMP; 1.9%). Overall, patients with MMAs were older (OR: 1.79, p = 5 × 10-5) and more likely to be males (OR: 2.45, p = 0.014). In particular, advancing age was associated with higher risk of drusen and ERM (OR: 1.80 and 4.26, p = 2 × 10-5 and 7 × 10-3, respectively). MMP prevalence declined with age (OR: 0.73, p = 0.015) and was associated with African-American ethnicity (OR: 15.0, p = 5 × 10-5). CONCLUSION: Unexpected or incidental MMAs are common in patients assessed with OCT in neuroimmunology practice, emphasizing the importance of comprehensive OCT image review for risk stratification and appropriate ophthalmology referral.

MRI shows a region-specific pattern of atrophy in spinocerebellar ataxia type 2.

In this study, we used manual delineation of high-resolution magnetic resonance imaging (MRI) to determine the spatial and temporal characteristics of the cerebellar atrophy in spinocerebellar ataxia type 2 (SCA2). Ten subjects with SCA2 were compared to ten controls. The volume of the pons, the total cerebellum, and the individual cerebellar lobules were calculated via manual delineation of structural MRI. SCA2 showed substantial global atrophy of the cerebellum. Furthermore, the degeneration was lobule specific, selectively affecting the anterior lobe, VI, Crus I, Crus II, VIII, uvula, corpus medullare, and pons, while sparing VIIB, tonsil/paraflocculus, flocculus, declive, tuber/folium, pyramis, and nodulus. The temporal characteristics differed in each cerebellar subregion: (1) duration of disease: Crus I, VIIB, VIII, uvula, corpus medullare, pons, and the total cerebellar volume correlated with the duration of disease; (2) age: VI, Crus II, and flocculus correlated with age in control subjects; and (3) clinical scores: VI, Crus I, VIIB, VIII, corpus medullare, pons, and the total cerebellar volume correlated with clinical scores in SCA2. No correlations were found with the age of onset. Our extrapolated volumes at the onset of symptoms suggest that neurodegeneration may be present even during the presymptomatic stages of disease. The spatial and temporal characteristics of the cerebellar degeneration in SCA2 are region specific. Furthermore, our findings suggest the presence of presymptomatic atrophy and a possible developmental component to the mechanisms of pathogenesis underlying SCA2. Our findings further suggest that volumetric analysis may aid in the development of a non-invasive, quantitative biomarker.

Principal component analysis of cerebellar shape on MRI separates SCA types 2 and 6 into two archetypal modes of degeneration.

Although "cerebellar ataxia" is often used in reference to a disease process, presumably there are different underlying pathogenetic mechanisms for different subtypes. Indeed, spinocerebellar ataxia (SCA) types 2 and 6 demonstrate complementary phenotypes, thus predicting a different anatomic pattern of degeneration. Here, we show that an unsupervised classification method, based on principal component analysis (PCA) of cerebellar shape characteristics, can be used to separate SCA2 and SCA6 into two classes, which may represent disease-specific archetypes. Patients with SCA2 (n=11) and SCA6 (n=7) were compared against controls (n=15) using PCA to classify cerebellar anatomic shape characteristics. Within the first three principal components, SCA2 and SCA6 differed from controls and from each other. In a secondary analysis, we studied five additional subjects and found that these patients were consistent with the previously defined archetypal clusters of clinical and anatomical characteristics. Secondary analysis of five subjects with related diagnoses showed that disease groups that were clinically and pathophysiologically similar also shared similar anatomic characteristics. Specifically, Archetype #1 consisted of SCA3 (n=1) and SCA2, suggesting that cerebellar syndromes accompanied by atrophy of the pons may be associated with a characteristic pattern of cerebellar neurodegeneration. In comparison, Archetype #2 was comprised of disease groups with pure cerebellar atrophy (episodic ataxia type 2 (n=1), idiopathic late-onset cerebellar ataxias (n=3), and SCA6). This suggests that cerebellar shape analysis could aid in discriminating between different pathologies. Our findings further suggest that magnetic resonance imaging is a promising imaging biomarker that could aid in the diagnosis and therapeutic management in patients with cerebellar syndromes.

Retinal and optic nerve head pathology in Susac's syndrome.

PURPOSE: This article describes the first retinal histopathologic findings in a patient with Susac's syndrome (SS). DESIGN: Observational case report. PARTICIPANT: A 51-year-old white woman diagnosed with SS. METHODS: Eyes from a 51-year-old white woman diagnosed with SS were obtained at autopsy. One retina was dissected and processed for adenosine diphosphatase (ADPase) flat embedding. Selected areas were processed further for transmission electron microscopy. MAIN OUTCOME MEASURES: Histopathologic examination using ADPase flat-embedding technique. RESULTS: There were vaso-occlusive changes in the retinal periphery resulting in small areas of capillary dropout. Cross-sections demonstrated serous filled spaces between the retinal blood vessels and the internal limiting membrane. Lumens adjacent to these spaces appeared compressed and sometimes closed, but without thrombosis. Decreased ADPase activity in some peripheral blood vessels suggested endothelial cell dysfunction and vaso-occlusion. In the optic nerve head, numerous corpora amylacea were observed in the vicinity of capillaries with thickened walls and narrow lumens. Transmission electron microscopy demonstrated thickened and amorphous vascular basal lamina and open endothelial cell junctions in some retinal blood vessels. CONCLUSIONS: The serous deposits with compression of retinal vessel lumens observed histologically probably represent the so-called string of pearls described clinically in SS. Chronic extension of these serous deposits along the vessel wall possibly are the cause of retinal arterial wall plaques as described by Gass and other investigators. In the optic nerve head, corpora amylacea are probably a result of microinfarcts resulting from optic nerve head capillary angiopathy. Accumulation of amorphous material in the basal lamina, loss of viable endothelial cells, and capillary dropout suggest that SS may be an endotheliopathy.

Contact focusing multimodal microprobes for ultraprecise laser tissue surgery.

Focusing of multimodal beams by chains of dielectric microspheres assembled directly inside the cores of hollow waveguides is studied by using numerical ray tracing. The device designs are optimized for laser surgery in contact mode with strongly absorbing tissue. By analyzing a broad range of parameters it is demonstrated that chains formed by three or five spheres with a refractive index of 1.65-1.75 provide a two-fold improvement in spatial resolution over single spheres at the cost of 0.2-0.4 attenuation in peak intensity of the central focused beam. Potential applications include ultra precise laser ablation or coagulation in the eye and brain, cellular surgery, and the coupling of light into photonic nanostructures.

The effect of acute superior oblique palsy on torsional optokinetic nystagmus in monkeys.

PURPOSE: To investigate the effects of acquired superior oblique palsy (SOP) and corrective strabismus surgery on torsional optokinetic nystagmus (tOKN) in monkeys. METHODS: The trochlear nerve was severed intracranially in two rhesus monkeys (M1 and M2). For each monkey, more than 4 months after the SOP, the ipsilateral inferior oblique muscle was denervated and extirpated. For M2, 4 months later, the contralateral inferior rectus muscle was recessed by 2 mm. tOKN was elicited during monocular viewing of a rotating stimulus that was rear projected onto a screen 43.5 cm in front of the animal. Angular rotation of the stimulus about the center was 40 deg/s clockwise or counterclockwise. RESULTS: The main findings after trochlear nerve sectioning were (1) the amplitude and peak velocity of torsional quick and slow phases of the paretic eye was less than that in the normal eye for both intorsion and extorsion, and (2) the vertical motion of the paretic eye increased during both torsional slow and quick phases. After corrective inferior oblique surgery, both of these effects were even greater. CONCLUSIONS: Acquired SOP and corrective inferior oblique-weakening surgery create characteristic patterns of change in tOKN that reflect alterations in the dynamic properties of the extraocular muscles involved in eye torsion. tOKN also provides information complementary to that provided by the traditional Bielschowsky head-tilt test and potentially can help distinguish among different causes of vertical ocular misalignment.

Acute superior oblique palsy in monkeys: I. Changes in static eye alignment.

PURPOSE: To investigate immediate and long-term changes in static ocular alignment with acute acquired superior oblique palsy (SOP) in monkeys. METHODS: The trochlear nerve was severed intracranially in two rhesus monkeys. After the surgery, the paretic eye was patched for 6 to 9 days, and then binocular viewing was allowed. Three-axis eye movements (horizontal, vertical, and torsional) were measured with binocular, dual search coils. Eye movements were recorded over a +/-20 degrees horizontal and vertical range of fixations before the lesion and then, beginning the first day after surgery. Changes in alignment with +/-30 degrees head tilt were also studied. RESULTS: The main findings were (1) misalignment (10-12 degrees vertical in adduction, down; 10-12 degrees torsional in abduction, down); (2) changes in vertical deviation (VD) with head tilt (Delta 2-6 degrees with left versus right 30 degrees tilt); and (3) changes in comitance and VD over time. During the early postlesion period, before binocular viewing was allowed, VD decreased and comitance improved. Once binocular viewing was allowed, VD increased and comitance worsened. CONCLUSIONS: Rhesus monkeys with induced SOP show a characteristic pattern of misalignment that helps define the ocular motor signature of acute denervation of the superior oblique muscle. The animals also showed striking changes over time in the amount and comitance of the vertical misalignment that depended on whether viewing was monocular or binocular, suggesting a role for proprioception in adaptation to misalignment with habitual monocular viewing.

Acute superior oblique palsy in monkeys: II. Changes in dynamic properties during vertical saccades.

PURPOSE: To investigate vertical and torsional eye motion during and immediately after vertical saccades with acute acquired superior oblique palsy (SOP) in monkeys. METHODS: The trochlear nerve was severed intracranially in two rhesus monkeys. After surgery, the paretic eye was patched for 6 to 9 days, and then binocular viewing was allowed. Three-axis eye movements (horizontal, vertical, and torsion) were measured with binocular, dual search coils. Eye movements were recorded before surgery and then beginning 2 to 3 days after surgery during 20 degrees vertical saccades over a +/-20 degrees horizontal and vertical range. RESULTS: The main findings were: (1) Saccade amplitude in the paretic eye (PE) was smaller than that of the normal eye (NE), especially for downward saccades with the PE in adduction; (2) vertical drift was backward after upward saccades with the PE in adduction or abduction, onward after downward saccades with the PE in adduction, but backward for downward saccades with the PE in abduction, drift time constants averaged 35 ms; (3) peak dynamic blip intrasaccadic torsion increased (relative extorsion), the most for upward saccades with the PE in abduction; (4) postsaccadic torsional drift increased (relative intorsion), the most for downward saccades with the PE in adduction; and (5) the peak velocity-amplitude relationship in vertical saccades was little affected, but the ratio between the peak velocity of the two eyes was a consistent indicator of the palsy. CONCLUSIONS: Rhesus monkeys with acute acquired SOP show characteristic changes in vertical and torsional movements during and immediately after vertical saccades that help define the ocular motor signature of denervation of the SO muscle. These dynamic changes were largely unrelated to the changes in static alignment over time, suggesting that static and dynamic disturbances in SOP are influenced by separate central mechanisms.

Quantitative eye movement recordings in a patient with acquired bilateral superior oblique palsy before and after a bilateral Harada-Ito procedure.

PURPOSE: We examined the effects of the Harada-Ito procedure on static and dynamic alignment in an adult with acquired bilateral superior oblique palsy (SOP). METHODS: 3D eye movements were recorded before and six weeks after a bilateral Harada-Ito procedure. Superior oblique muscle (SOM) size and contractility were assessed with orbital imaging. RESULTS: On MRI, the left SOM was smaller than the right. Little contractile thickening was present in down gaze for either eye. Preoperatively, the patient had a hypertropia: 1.9 degrees right hypertropia (at down 20 degrees , left 20 degrees ) and 6.4 degrees left hypertropia (at down 20 degrees , right 20 degrees ). Postoperatively, the vertical tropia in all positions was < 1 degrees . Listing's primary position rotated toward straight ahead for the RE but was unchanged for the LE. Postoperatively, for 40 degrees upward saccades peak dynamic intrasaccadic extorsion decreased by 2.2-3.2 degrees for both eyes and for 40 degrees downward saccades by 2.3-3.6 degrees for the RE but was unchanged for the LE. Saccade conjugacy improved and post-saccadic drift lessened for all vertical saccades. CONCLUSIONS: The Harada-Ito procedure produced striking improvements in static and dynamic alignment in bilateral SOP. Some changes were binocular (decreased post-saccadic drift, improved saccade conjugacy, less dynamic extorsion for upward saccades) but others were much greater in the less paretic eye (torsional gradients from up to down gaze, less dynamic extorsion for downward saccades). Both central adaptive and peripheral mechanical changes explain these findings. Our results also imply that the Harada-Ito procedure has more effect when there is residual function of the SOM.

Improving graph-based OCT segmentation for severe pathology in Retinitis Pigmentosa patients.

Three dimensional segmentation of macular optical coherence tomography (OCT) data of subjects with retinitis pigmentosa (RP) is a challenging problem due to the disappearance of the photoreceptor layers, which causes algorithms developed for segmentation of healthy data to perform poorly on RP patients. In this work, we present enhancements to a previously developed graph-based OCT segmentation pipeline to enable processing of RP data. The algorithm segments eight retinal layers in RP data by relaxing constraints on the thickness and smoothness of each layer learned from healthy data. Following from prior work, a random forest classifier is first trained on the RP data to estimate boundary probabilities, which are used by a graph search algorithm to find the optimal set of nine surfaces that fit the data. Due to the intensity disparity between normal layers of healthy controls and layers in various stages of degeneration in RP patients, an additional intensity normalization step is introduced. Leave-one-out validation on data acquired from nine subjects showed an average overall boundary error of 4.22 µm as compared to 6.02 µm using the original algorithm.

Lack of Evidence for Vasoactive and Inflammatory Mediators in the Promotion of Macular Edema Associated with Epiretinal Membranes.

The development of symptoms in patients with epiretinal membranes (ERMs) often corresponds with the accumulation of interstitial fluid in the retina [i.e., the development of macular edema, (ME)]. To explore the potential value of pharmacologic therapeutic options to treat ME in patients with ERMs, we examine here the expression of vasoactive and inflammatory mediators in the vitreous of patients with idiopathic ERMs. We observed that vitreous concentrations of classic vasoactive factors (e.g., vascular endothelial growth factor) were similar in ERM patients with ME compared to controls. Using an array assessing the expression of 102 inflammatory cytokines we similarly did not observe a marked difference in cytokine expression in the vitreous of most ERM patients with ME compared to control patients. While the array data did implicate a group of inflammatory cytokines that were elevated in a subset of ERM patients who had severe ME (central subfield thickness ≥450 µm on spectral domain optical coherence tomography), expression of 3 of these inflammatory cytokines, all previously implicated in the promotion of ME in ischemic retinal disease, were not elevated by quantitative enzyme-linked immunosorbent assay. We conclude that therapies modulating vasoactive mediators or inflammatory cytokines may not affect ME in ERM patients.

Optical coherence tomography of enucleated human eye specimens with histological correlation: origin of the outer "red line".

PURPOSE: To further define the origin of the "outer red line" (ORL) present in retinal optical coherence tomograms. DESIGN: Laboratory investigation. METHODS: Eleven formalin-fixed caps of seven human eyes previously enucleated for choroidal melanoma at the Wilmer Eye Institute were studied. The ORL evaluation consisted of sequential, surgical elimination of the retinal pigment epithelium, Bruch's membrane (BM), and choroid in separate, but adjacent, areas. Optical coherence tomography (OCT) images through each of these areas were correlated with corresponding histologic sections. The relative contribution of the retinal pigment epithelium, BM, and choroid to the ORL in retinal OCT3 images was evaluated. RESULTS: In the specimens examined, the ORL correlated anatomically with a highly reflective optical surface at the level of the outer retina, and did not appear to represent a specific anatomic layer. The reflecting layers appeared to be composed of the retinal pigment epithelium, BM, and inner choroid. The relative contribution of BM together with the inner choroid to the ORL appeared greater than that of the retinal pigment epithelium. CONCLUSIONS: This study suggests that the ORL present in retinal OCT3 images and generally associated with the retinal pigment epithelium/BM/inner choroidal complex appears to indicate a highly reflective optical surface which, when eye layers are normally configured, represents this complex of anatomic structures with a predominant contribution from BM and inner choroid. The findings of this study suggest a potential role for OCT in the eye pathology laboratory.

Comparison of retrobulbar and sub-Tenon's capsule injection of local anesthetic in vitreoretinal surgery.

OBJECTIVE: To compare the efficacy and efficiency of retrobulbar versus sub-Tenon's capsule injection of local anesthetic in vitreoretinal surgery. DESIGN: Prospective, randomized, double-masked clinical trial. PARTICIPANTS AND INTERVENTION: Sixty-four eyes from 61 patients undergoing vitreoretinal surgery were randomized to receive either retrobulbar or sub-Tenon's capsule injection of 5 ml of a 50:50 mixture of 4% lidocaine and 0.75% bupivacaine. MAIN OUTCOME MEASURES: The primary outcome measured was intraoperative eye pain, which was rated by patients in both groups using an 11-point (0-10) numerical visual analogue scale immediately after surgery and again the next morning. The surgeons indicated whether they perceived patient discomfort during 4 different stages of the operation: opening of the conjunctiva, vitrectomy (if performed), placement of scleral buckle (if performed), and closing of the conjunctiva. The preincision time, need for supplemental local anesthesia, and use of IV sedation for additional pain control were compared between the two groups. RESULTS: Thirty-four eyes were randomized to retrobulbar injections, and 30 eyes were randomized to sub-Tenon's capsule injections. There was no significant difference in patient-reported intraoperative pain scores between the retrobulbar and sub-Tenon's capsule groups when assessed immediately after surgery (median, 2.0 vs. 2.0; P = 0.52) or the next day (median, 2.0 vs. 1.0; P = 0.26). The surgeons reported no difference between the two groups in terms of the percentages of patients with pain during opening of the conjunctiva (20.6% vs. 3.3%; P = 0.058), vitrectomy (31% vs. 32%; P = 1.00), placement of scleral buckle (33.3% vs. 40%; P = 1.00), and closing of the conjunctiva (26.5% vs. 26.7%; P = 1.00). There was a suggestion that preincision time was longer in the sub-Tenon's capsule group. Approximately equal percentages of patients in each group required supplemental local anesthesia (38% vs. 37%; P = 0.90) or IV medication (85% vs. 70%; P = 0.14) for pain control. CONCLUSIONS: Sub-Tenon's capsule injection of local anesthetic seems as effective as retrobulbar injection at controlling intraoperative pain in vitreoretinal surgery.

Neuropilin-1 expression by endothelial cells and retinal pigment epithelial cells in choroidal neovascular membranes.

PURPOSE: To determine if vascular endothelial growth factor (VEGF) coreceptor neuropilin-1 (NP-1) is expressed in choroidal neovascularization (CNV) and to localize the expression. DESIGN: Laboratory investigation. METHODS: Six CNV membranes (CNVMs) obtained from patients with subfoveal CNV attributable to age-related macular degeneration (AMD) underwent immunohistochemistry for VEGF receptor-2 (VEGFR-2) and NP-1. The positive cell types were identified by double staining with anticytokeratin, anti-CD31, and antismooth muscle actin (SMA). RESULTS: Immunohistochemical staining revealed positivity for VEGFR-2 and NP-1 in all six CNVMs. Both receptors were strongly expressed by new choroidal endothelial cell forming vessels and CD-31-positive cells in the nonvascular area. They were also expressed in the pigmented retinal pigment epithelial layer and by cytokeratin-positive, nonpigmented retinal pigment epithelium cells in the nonvascular area. The nonpigmented retinal pigment epithelium cells positive for VEGFR-2 and NP-1 were highly colocalized with SMA. CONCLUSIONS: The presence of both VEGF and NP-1 suggest that NP-1 may play a role in the evolution of CNV in AMD.

Mechanisms of Vertical Fusional Vergence in Patients With "Congenital Superior Oblique Paresis" Investigated With an Eye-Tracking Haploscope.

PURPOSE: To determine the mechanisms of vertical fusional vergence in patients with "congenital unilateral superior oblique paresis" (SOP) and to discuss the implications of these mechanisms. METHODS: Eleven patients were examined with our eye-tracking haploscope. RESULTS: Three different fusion mechanisms were found, producing significantly different cyclovergence to vertical vergence ratios (P < 0.05): primary use of the vertical rectus muscles in seven patients (ratio: 0.36 ± 1.6), primary use of the oblique muscles in one patient (0.04), and use of the superior oblique muscle in the higher eye and the superior rectus muscle in the lower eye in three patients (1.15 ± 0.32). Lancaster red-green testing showed alignment differences among these groups, primarily differences in amount of subjective extorsion between the two eyes in straight-ahead gaze: The patient with oblique-muscle-mediated fusion showed essentially no subjective extorsion (0.5°), the patients with vertical-rectus-muscle-mediated vertical fusion showed a mean ± SD subjective extorsion of 3.6° ± 1.4°, and the patients with the mixed (oblique/rectus) fusion mechanism showed 7.0° ± 1.7° (P < 0.05). CONCLUSIONS: The choice of fusion mechanism may be a function of how much intorting effect is needed. Use of the oblique muscles bilaterally causes the least intorting effect, use of the vertical rectus muscles bilaterally adds more intorting effect, and activation of the "paretic" superior oblique muscle in the higher eye and the superior rectus muscle in the lower eye provides the greatest intorting effect. Subclassifying "congenital SOP" in this way (in which the "paretic" muscle may remain functional in many cases) may help guide its optimal surgical correction.

Longitudinal graph-based segmentation of macular OCT using fundus alignment.

Segmentation of retinal layers in optical coherence tomography (OCT) has become an important diagnostic tool for a variety of ocular and neurological diseases. Currently all OCT segmentation algorithms analyze data independently, ignoring previous scans, which can lead to spurious measurements due to algorithm variability and failure to identify subtle changes in retinal layers. In this paper, we present a graph-based segmentation framework to provide consistent longitudinal segmentation results. Regularization over time is accomplished by adding weighted edges between corresponding voxels at each visit. We align the scans to a common subject space before connecting the graphs by registering the data using both the retinal vasculature and retinal thickness generated from a low resolution segmentation. This initial segmentation also allows the higher dimensional temporal problem to be solved more efficiently by reducing the graph size. Validation is performed on longitudinal data from 24 subjects, where we explore the variability between our longitudinal graph method and a cross-sectional graph approach. Our results demonstrate that the longitudinal component improves segmentation consistency, particularly in areas where the boundaries are difficult to visualize due to poor scan quality.

Automatic segmentation of microcystic macular edema in OCT.

Microcystic macular edema (MME) manifests as small, hyporeflective cystic areas within the retina. For reasons that are still largely unknown, a small proportion of patients with multiple sclerosis (MS) develop MME-predominantly in the inner nuclear layer. These cystoid spaces, denoted pseudocysts, can be imaged using optical coherence tomography (OCT) where they appear as small, discrete, low intensity areas with high contrast to the surrounding tissue. The ability to automatically segment these pseudocysts would enable a more detailed study of MME than has been previously possible. Although larger pseudocysts often appear quite clearly in the OCT images, the multi-frame averaging performed by the Spectralis scanner adds a significant amount of variability to the appearance of smaller pseudocysts. Thus, simple segmentation methods only incorporating intensity information do not perform well. In this work, we propose to use a random forest classifier to classify the MME pixels. An assortment of both intensity and spatial features are used to aid the classification. Using a cross-validation evaluation strategy with manual delineation as ground truth, our method is able to correctly identify 79% of pseudocysts with a precision of 85%. Finally, we constructed a classifier from the output of our algorithm to distinguish clinically identified MME from non-MME subjects yielding an accuracy of 92%.