Faculty Bibliography

OBJECTIVE: To introduce new corneal high-speed, ultra-high-resolution optical coherence tomography (hsUHR-OCT) technology that improves the evaluation of complicated and uncomplicated cataract, corneal, and refractive surgical procedures. DESIGN: This case series included a control subject and 9 eyes of 8 patients who had undergone phacoemulsification, Descemet membrane stripping endokeratoplasty, corneal implantation for keratoconus, and complicated and uncomplicated laser in situ keratomileusis. These eyes underwent imaging using a prototype ophthalmic hsUHR-OCT system. All the scans were compared with conventional slitlamp biomicroscopy. RESULTS: Cross-sectional hsUHR-OCT imaging allowed in vivo differentiation of corneal layers and existing pathologic abnormalities at ultrahigh axial image resolution. These images illustrate the various incisional and refractive interfaces created with corneal procedures. CONCLUSIONS: The magnified view of the cornea using hsUHR-OCT is helpful in conceptualizing and understanding basic and complicated clinical pathologic features; hsUHR-OCT has the potential to become a powerful, noninvasive clinical corneal imaging modality that can enhance surgical management. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00343473.

PURPOSE: To determine the retinal nerve fiber layer (RNFL) thickness profile in the peripapillary region of healthy eyes. METHODS: Three-dimensional, Fourier/spectral domain optical coherence tomography (OCT) data were obtained as raster scan data (512 x 180 axial scans in a 6 x 6-mm region centered on the optic nerve head [ONH]) with high-speed, ultrahigh-resolution OCT (hsUHR-OCT) from 12 healthy subjects. RNFL thickness was measured on this three-dimensional data set with an in-house software program. The disc margin was defined subjectively in each image and RNFL thickness profiles relative to distance from the disc center were computed for quadrants and clock hours. A mixed-effects model was used to characterize the slope of the profiles. RESULTS: Thickness profiles in the superior, inferior, and temporal quadrants showed an initial increase in RNFL thickness, an area of peak thickness, and a linear decrease as radial distance from the disc center increased. The nasal quadrant showed a constant linear decay without the initial RNFL thickening. A mixed-effects model showed that the slopes of the inferior, superior, and nasal quadrants differed significantly from the temporal slope (P = 0.0012, P = 0.0003, and P = 0.0004, respectively). CONCLUSIONS: RNFL thickness is generally inversely related to the distance from the ONH center in the peripapillary region of healthy subjects, as determined by hsUHR-OCT. However, several areas showed an initial increase in RNFL, followed by a peak and a gradual decrease.

We use Fourier domain optical coherence tomography (OCT) data to assess retinal blood oxygen saturation. Three-dimensional disk-centered retinal tissue volumes were assessed in 17 normal healthy subjects. After removing DC and low-frequency a-scan components, an OCT fundus image was created by integrating total reflectance into a single reflectance value. Thirty fringe patterns were sampled; 10 each from the edge of an artery, adjacent tissue, and the edge of a vein, respectively. A-scans were recalculated, zeroing the DC term in the power spectrum, and used for analysis. Optical density ratios (ODRs) were calculated as ODR(Art)=ln(Tissue(855)Art(855))ln(Tissue(805)Art(805)) and ODR(Vein)=ln(Tissue(855)Vein(855))ln(Tissue(805)Vein(805)) with Tissue, Art, and Vein representing total a-scan reflectance at the 805- or 855-nm centered bandwidth. Arterial and venous ODRs were compared by the Wilcoxon signed rank test. Arterial ODRs were significantly greater than venous ODRs (1.007+/-2.611 and -1.434+/-4.310, respectively; p=0.0217) (mean+/-standard deviation). A difference between arterial and venous blood saturation was detected. This suggests that retinal oximetry may possibly be added as a metabolic measurement in structural imaging devices.

OBJECTIVES: To compare structural changes in the retina seen on high-speed ultra-high-resolution optical coherence tomography (hsUHR-OCT) with multifocal electroretinography (mfERG) and automated visual fields in patients receiving hydroxychloroquine. METHODS: Fifteen patients receiving hydroxychloroquine were evaluated clinically with hsUHR-OCT, mfERG, and automated visual fields. Six age-matched subjects were imaged with hsUHR-OCT and served as controls. RESULTS: Distinctive discontinuity of the perifoveal photoreceptor inner segment/outer segment junction and thinning of the outer nuclear layer were seen with hsUHR-OCT in patients with mild retinal toxic effects. Progression to complete loss of the inner segment/outer segment junction and hyperscattering at the outer segment level were seen in more advanced cases. The mfERG abnormalities correlated with the hsUHR-OCT findings. Asymptomatic patients had normal hsUHR-OCT and mfERG results. CONCLUSION: Distinctive abnormalities in the perifoveal photoreceptor inner segment/outer segment junction were seen on hsUHR-OCT in patients receiving hydroxychloroquine who also were symptomatic and had abnormalities on automated visual fields and mfERG.

We present a computationally efficient, semiautomated method for analysis of posterior retinal layers in three-dimensional (3-D) images obtained by spectral optical coherence tomography (SOCT). The method consists of two steps: segmentation of posterior retinal layers and analysis of their thickness and distance from an outer retinal contour (ORC), which is introduced to approximate the normal position of external interface of the healthy retinal pigment epithelium (RPE). The algorithm is shown to effectively segment posterior retina by classifying every pixel in the SOCT tomogram using the similarity of its surroundings to a reference set of model pixels from user-selected area(s). Operator intervention is required to assess the quality of segmentation. Thickness and distance maps from the segmented layers and their analysis are presented for healthy and pathological retinas.

PURPOSE: To describe two cases of peripapillary retinal schisis in patients with glaucoma without evidence of optic nerve pits, pseudopits, or X-linked retinoschisis. DESIGN: Two observational case reports and literature review. METHODS: Imaging of the peripapillary nerve fiber layer and schisis cavities was completed in two patients, and one patient was followed over time. RESULTS: The first patient, diagnosed with narrow angle glaucoma, was noted to have peripapillary schisis in the right eye with matching changes on visual field and optical coherence tomographic (OCT) results. Follow-up examination revealed that the schisis disappeared in the right eye while appearing in the left. The findings were verified with high-speed ultra-high-resolution OCT performed in both eyes. The second case involved a patient with anatomically narrow angles, high intraocular pressure (IOP), and peripapillary schisis extending into the macula. CONCLUSIONS: Peripapillary retinoschisis may represent a unique sequelae of intraocular fluctuations in patients with uncontrolled glaucoma. Further studies are needed to better understand this disease process.

Excessive retinal vascular permeability contributes to the pathogenesis of proliferative diabetic retinopathy and diabetic macular edema, leading causes of vision loss in working-age adults. Using mass spectroscopy-based proteomics, we detected 117 proteins in human vitreous and elevated levels of extracellular carbonic anhydrase-I (CA-I) in vitreous from individuals with diabetic retinopathy, suggesting that retinal hemorrhage and erythrocyte lysis contribute to the diabetic vitreous proteome. Intravitreous injection of CA-I in rats increased retinal vessel leakage and caused intraretinal edema. CA-I-induced alkalinization of vitreous increased kallikrein activity and its generation of factor XIIa, revealing a new pathway for contact system activation. CA-I-induced retinal edema was decreased by complement 1 inhibitor, neutralizing antibody to prekallikrein and bradykinin receptor antagonism. Subdural infusion of CA-I in rats induced cerebral vascular permeability, suggesting that extracellular CA-I could have broad relevance to neurovascular edema. Inhibition of extracellular CA-I and kallikrein-mediated innate inflammation could provide new therapeutic opportunities for the treatment of hemorrhage-induced retinal and cerebral edema.

PURPOSE: To demonstrate high-speed, ultrahigh-resolution optical coherence tomography (OCT) for noninvasive, in vivo, three-dimensional imaging of the retina in rat and mouse models. METHODS: A high-speed, ultrahigh-resolution OCT system using spectral, or Fourier domain, detection has been developed for small animal retinal imaging. Imaging is performed with a contact lens and postobjective scanning. An axial image resolution of 2.8 mum is achieved with a spectrally broadband superluminescent diode light source with a bandwidth of approximately 150 nm at approximately 900-nm center wavelength. Imaging can be performed at 24,000 axial scans per second, which is approximately 100 times faster than previous ultrahigh-resolution OCT systems. High-definition and three-dimensional retinal imaging is performed in vivo in mouse and rat models. RESULTS: High-speed, ultrahigh-resolution OCT enabled high-definition, high transverse pixel density imaging of the murine retina and visualization of all major intraretinal layers. Raster scan protocols enabled three-dimensional volumetric imagingand comprehensive retinal segmentation algorithms allowed measurement of retinal layers. An OCT fundus image, akin to a fundus photograph was generated by axial summation of three-dimensional OCT data, thus enabling precise registration of OCT measurements to retinal fundus features. CONCLUSIONS: High-speed, ultrahigh-resolution OCT enables imaging of retinal architectural morphology in small animal models. OCT fundus images allow precise registration of OCT images and repeated measurements with respect to retinal fundus features. Three-dimensional OCT imaging enables visualization and quantification of retinal structure, which promises to allow repeated, noninvasive measurements to track disease progression, thereby reducing the need for killing the animal for histology. This capability can accelerate basic research studies in rats and mice and their translation into clinical patient care.