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.

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.

Widefield Fundus Fluorescein Angiography Features of Uveitis Associated with Juvenile Idiopathic Arthritis.

PURPOSE: To evaluate the wide-field fundus fluorescein angiography (WFA) characteristics of uveitis associated with juvenile idiopathic arthritis (JIA-uveitis). METHODS: Retrospective review of records. WFA with Spectralis (Heidelberg) of JIA-uveitis patients were analyzed using the scoring system by Angiography Scoring for Uveitis Nomenclature. RESULTS: Thirty-seven eyes of 20 patients were studied. A total score of at least 1 was noted in 27 eyes (72.97%). WFA features included optic disc hyperfluorescence (51.35%), macular leakage (27.03%), retinal vascular staining/leakage at posterior pole (27.03%) and peripheral retina (64.86%), capillary leakage at the posterior pole (37.84%), and peripheral retina (59.46%). A decision to change the management plan was made in 8 of 9 patients with bilateral quiet anterior chambers after WFA results. CONCLUSION: More than 70% of JIA-uveitis eyes showed some WFA-evidence of posterior segment inflammation, which changed the course of therapy for a major proportion of patients with no clinically active anterior chamber inflammation.

RAPIDLY PROGRESSIVE NEOVASCULAR GLAUCOMA FROM CYTOMEGALOVIRUS RETINITIS IN A NON-HUMAN IMMUNODEFICIENCY VIRUS PATIENT.

PURPOSE: To describe a case of neovascular glaucoma from cytomegalovirus (CMV) retinitis in a human immunodeficiency virus-negative patient with immunosuppression after stem-cell transplant for multiple myeloma. METHODS: Retrospective case report. RESULTS: A 71-year-old man on monthly infusion of daratumumab for multiple myeloma after stem-cell transplant presenting with a 2-week history of floaters, photophobia, and blurry vision was found to have polymerase chain reaction-confirmed CMV retinitis associated with diffuse occlusive vasculitis. The patient was human immunodeficiency virus negative with a CD4 count of 450/mm3. Despite immediate aggressive treatment, the patient developed neovascular glaucoma with poor visual outcome. CONCLUSION: Cytomegalovirus retinitis in human immunodeficiency virus-negative patients is becoming more prevalent with increasing use of systemic immunosuppression therapy for various reasons. Patients with non-human immunodeficiency virus related CMV retinitis can have severe ischemia atypical of the classic CMV retinitis and should be followed closely for neovascularization.

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.

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.

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.

Compartmental Innervation of the Superior Oblique Muscle in Mammals.

PURPOSE: Intramuscular innervation of mammalian horizontal rectus extraocular muscles (EOMs) is compartmental. We sought evidence of similar compartmental innervation of the superior oblique (SO) muscle. METHODS: Three fresh bovine orbits and one human orbit were dissected to trace continuity of SO muscle and tendon fibers to the scleral insertions. Whole orbits were also obtained from four humans (two adults, a 17-month-old child, and a 33-week stillborn fetus), two rhesus monkeys, one rabbit, and one cow. Orbits were formalin fixed, embedded whole in paraffin, serially sectioned in the coronal plane at 10-µm thickness, and stained with Masson trichrome. Extraocular muscle fibers and branches of the trochlear nerve (CN4) were traced in serial sections and reconstructed in three dimensions. RESULTS: In the human, the lateral SO belly is in continuity with tendon fibers inserting more posteriorly on the sclera for infraducting mechanical advantage, while the medial belly is continuous with anteriorly inserting fibers having mechanical advantage for incycloduction. Fibers in the monkey superior SO insert more posteriorly on the sclera to favor infraduction, while the inferior portion inserts more anteriorly to favor incycloduction. In all species, CN4 bifurcates prior to penetrating the SO belly. Each branch innervates a nonoverlapping compartment of EOM fibers, consisting of medial and lateral compartments in humans and monkeys, and superior and inferior compartments in cows and rabbits. CONCLUSIONS: The SO muscle of humans and other mammals is compartmentally innervated in a manner that could permit separate CN4 branches to selectively influence vertical versus torsional action.

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.

Scatter Photocoagulation Does Not Reduce Macular Edema or Treatment Burden in Patients with Retinal Vein Occlusion: The RELATE Trial.

PURPOSE: To determine whether scatter and grid laser photocoagulation (laser) adds benefit to ranibizumab injections in patients with macular edema from retinal vein occlusion (RVO) and to compare 0.5-mg with 2.0-mg ranibizumab. DESIGN: Randomized, double-masked, controlled clinical trial. PARTICIPANTS: Thirty-nine patients with central RVO (CRVO) and 42 with branch RVO (BRVO). METHODS: Subjects were randomized to 0.5 mg or 2.0 mg ranibizumab every 4 weeks for 24 weeks and re-randomized to pro re nata ranibizumab plus laser or ranibizumab alone. MAIN OUTCOME MEASURES: Mean change from baseline best-corrected visual acuity (BCVA) at week 24 for BCVA at weeks 48, 96, and 144 for second randomization. RESULTS: Mean improvement from baseline BCVA at week 24 was 15.5 and 15.8 letters in the 0.5-mg and 2.0-mg CRVO groups, and 12.1 and 14.6 letters in the 0.5-mg and 2.0-mg BRVO groups. For CRVO, but not BRVO, there was significantly greater reduction from baseline mean central subfield thickness (CST) in the 2.0-mg versus 0.5-mg group (396.1 vs. 253.5 µm; P = 0.03). For the second randomization in CRVO patients, there was no significant difference from week 24 BCVA in the ranibizumab plus laser versus the ranibizumab only groups at week 48 (-3.3 vs. 0.0 letters), week 96 (+0.69 vs. -1.6 letters), or week 144 (+0.4 vs. -6.7 letters), and a significant increase from week 24 mean CST at week 48 (+94.7 vs. +15.2 µm; P = 0.05) but not weeks 96 or 144. For BRVO, there was a significant reduction from week 24 mean BCVA in ranibizumab plus laser versus ranibizumab at week 48 (-7.5 vs. +2.8; P < 0.01) and week 96 (-2.0 vs. +4.8; P < 0.03), but not week 144, and there were no differences in mean CST change from week 24 at weeks 48, 96, or 144. Laser failed to increase edema resolution or to reduce the ranibizumab injections between weeks 24 and 144. CONCLUSIONS: In patients with macular edema resulting from RVO, there was no short-term clinically significant benefit from monthly injections of 2.0-mg versus 0.5-mg ranibizumab injections and no long-term benefit in BCVA, resolution of edema, or number of ranibizumab injections obtained by addition of laser treatment to ranibizumab.

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.

Pro-Permeability Factors After Dexamethasone Implant in Retinal Vein Occlusion; the Ozurdex for Retinal Vein Occlusion (ORVO) Study.

PURPOSE: To correlate aqueous vasoactive protein changes with macular edema after dexamethasone implant in retinal vein occlusion (RVO). DESIGN: Prospective, interventional case series. METHODS: Twenty-three central RVO (CRVO) and 17 branch RVO (BRVO) subjects with edema despite prior anti-vascular endothelial growth factor (VEGF) treatment had aqueous taps at baseline and 4 and 16 weeks after dexamethasone implant. Best-corrected visual acuity (BCVA) and center subfield thickness were measured every 4 weeks. Aqueous vasoactive protein levels were measured by protein array or enzyme-linked immunosorbent assay. RESULTS: Thirty-two vasoactive proteins were detected in aqueous in untreated eyes with macular edema due to RVO. Reduction in excess foveal thickness after dexamethasone implant correlated with reduction in persephin and pentraxin 3 (Pearson correlation coefficients = 0.682 and 0.638, P = .014 and P = .003). Other protein changes differed among RVO patients as edema decreased, but ≥50% of patients showed reductions in hepatocyte growth factor, endocrine gland VEGF, insulin-like growth factor binding proteins, or endostatin by ≥30%. Enzyme-linked immunosorbent assay in 18 eyes (12 CRVO, 6 BRVO) showed baseline levels of hepatocyte growth factor and VEGF of 168.2 ± 20.1 pg/mL and 78.7 ± 10.0 pg/mL, and each was reduced in 12 eyes after dexamethasone implant. CONCLUSIONS: Dexamethasone implants reduce several pro-permeability proteins providing a multitargeted approach in RVO. No single protein in addition to VEGF can be implicated as a contributor in all patients. Candidates for contribution to chronic edema in subgroups of patients that deserve further study include persephin, hepatocyte growth factor, and endocrine gland VEGF.

Characterization of Vestibulopathy in Individuals with Type 2 Diabetes Mellitus.

OBJECTIVE: Previous observational studies suggest higher rates of vestibular dysfunction among patients with type 2 diabetes mellitus (DM) compared with those without diabetes. This study aims to functionally localize vestibular dysfunction in adults with type 2 DM. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary academic medical center. SUBJECTS AND METHODS: Adults 50 years of age and older with ≥10-year history of type 2 DM were recruited (December 2011-February 2013, n = 25). Vestibular function was assessed by cervical and ocular vestibular-evoked myogenic potentials (VEMPs), testing the saccule and utricle, respectively. Head thrust dynamic visual acuity testing assessed semicircular canal (SCC) function in all canal planes. Results were compared with nondiabetic age-matched controls (n = 25). RESULTS: Subjects were 64.7 ± 7.6 years old, were 40% female, and had a mean hemoglobin A1c of 8.3% ± 1.7%. SCC dysfunction was more common than otoconial organ dysfunction, with 70% of subjects with DM demonstrating impaired performance of at least 1 SCC (ΔlogMAR ≥0.18) and 50% demonstrating otoconial organ impairment (absent ocular VEMP and/or cervical VEMP). Adults with type 2 DM had poorer lateral and superior SCC performance (P < .05) but similar posterior SCC performance compared with controls (P = .16). Both cervical VEMP peak-to-peak amplitude and ocular VEMP n1 amplitude were also decreased with diabetes (P < .01). CONCLUSION: Adults with type 2 DM have poorer performance on tests of vestibular function related to both SCC and otoconial organ function compared with nondiabetic age-matched adults. Future studies are needed to better understand the relationship between vestibular function and functional disability in persons with diabetes.

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%.

Regression of choroidal neovascularization results in macular atrophy in anti-vascular endothelial growth factor-treated eyes.

PURPOSE: To determine the incidence and progression of macular atrophy in patients with neovascular age-related macular degeneration (AMD) treated with vascular endothelial growth factor (VEGF) antagonists. DESIGN: Retrospective interventional case series. METHODS: All patients with neovascular AMD treated by the same physician during a 12-month period of ascertainment had all images from their entire follow-up period evaluated, and areas of retina that developed atrophy were compared to the same areas prior to the onset of anti-VEGF treatment. Longitudinal measurements of retinal atrophy were made. RESULTS: In 39 patients, 52 eyes with neovascular AMD were identified. We excluded 5 eyes from analysis (4 had retinal pigment epithelium tears, and 1 had a laser scar). Fundus photographs of the remaining eyes showed that 18/47 eyes (38%) contained hypopigmented areas suggestive of atrophy within the macula at some time during follow-up. Spectral-domain optical coherence tomography confirmed that these areas had loss of retinal pigmented epithelium and ellipsoids zones, with or without subretinal material suggestive of subretinal fibrosis. Comparison of fundus photographs with fluorescein angiograms showed that in 13/18 eyes (72%), atrophy developed in areas previously occupied by choroidal neovascularization, and the other 5 eyes had atrophy prior to the onset of anti-VEGF treatment. The mean (± standard deviation) rate of increase in pure atrophic areas (no subretinal material) was 0.7 ± 0.8 mm(2) per year, with a range of 0.01-2.6 mm(2)/year. CONCLUSION: Treatment of neovascular AMD with a VEGF-neutralizing protein can result in regression of choroidal neovascularization, which is sometimes associated with atrophy of overlying retina.

Analysis of macular OCT images using deformable registration.

Optical coherence tomography (OCT) of the macula has become increasingly important in the investigation of retinal pathology. However, deformable image registration, which is used for aligning subjects for pairwise comparisons, population averaging, and atlas label transfer, has not been well-developed and demonstrated on OCT images. In this paper, we present a deformable image registration approach designed specifically for macular OCT images. The approach begins with an initial translation to align the fovea of each subject, followed by a linear rescaling to align the top and bottom retinal boundaries. Finally, the layers within the retina are aligned by a deformable registration using one-dimensional radial basis functions. The algorithm was validated using manual delineations of retinal layers in OCT images from a cohort consisting of healthy controls and patients diagnosed with multiple sclerosis (MS). We show that the algorithm overcomes the shortcomings of existing generic registration methods, which cannot be readily applied to OCT images. A successful deformable image registration algorithm for macular OCT opens up a variety of population based analysis techniques that are regularly used in other imaging modalities, such as spatial normalization, statistical atlas creation, and voxel based morphometry. Examples of these applications are provided to demonstrate the potential benefits such techniques can have on our understanding of retinal disease. In particular, included is a pilot study of localized volumetric changes between healthy controls and MS patients using the proposed registration algorithm.

Multiple-object geometric deformable model for segmentation of macular OCT.

Optical coherence tomography (OCT) is the de facto standard imaging modality for ophthalmological assessment of retinal eye disease, and is of increasing importance in the study of neurological disorders. Quantification of the thicknesses of various retinal layers within the macular cube provides unique diagnostic insights for many diseases, but the capability for automatic segmentation and quantification remains quite limited. While manual segmentation has been used for many scientific studies, it is extremely time consuming and is subject to intra- and inter-rater variation. This paper presents a new computational domain, referred to as flat space, and a segmentation method for specific retinal layers in the macular cube using a recently developed deformable model approach for multiple objects. The framework maintains object relationships and topology while preventing overlaps and gaps. The algorithm segments eight retinal layers over the whole macular cube, where each boundary is defined with subvoxel precision. Evaluation of the method on single-eye OCT scans from 37 subjects, each with manual ground truth, shows improvement over a state-of-the-art method.

Comparison of time- and spectral-domain optical coherence tomography in management of diabetic macular edema.

PURPOSE: Some clinical trials that proved the benefits of anti-VEGF therapy for diabetic macular edema (DME) based retreatment decisions on visual acuity and time-domain ocular coherence tomography (TD-OCT) central subfield thickness changes since the last treatment. This study assessed the impact of TD-OCT followed by spectral domain (SD)-OCT on as needed treatment decision-making in the management of DME with anti-VEGF medications. METHODS: Patients previously treated for DME with anti-VEGF medications in the Retina Division of the Wilmer Eye Institute, following an institutional review board-approved informed consent process, underwent clinical examination, TD-, and SD-OCT imaging. Their retina specialists recorded whether additional anti-VEGF therapy was recommended and their level of certainty in the decision after performing a clinical examination and reviewing a TD-OCT, and then again after reviewing a SD-OCT. RESULTS: Data were collected for 129 treatment decision pairs involving 67 eyes from 46 subjects. Nonconcordant decisions occurred in 9 (7%) treatment decision pairs. In 7 of these (5%, 95% confidence interval [CI]: 2%-11%), the addition of SD-OCT changed the retina specialist's decision from not recommending to recommending retreatment. The addition of SD-OCT increased the certainty of the retina specialist in 36% (95% CI: 27%-45%) of all treatment decision pairs. CONCLUSIONS: Spectral-domain OCT does not appear to change the ultimate treatment decision or increase the level of certainty of the retina specialist relative to TD-OCT in most cases of DME under anti-VEGF management in clinical practice. The few nonconcordant decisions appear to trend toward recommending more anti-VEGF therapy following SD-OCT.