Andrew W. Francis

Morphometric Analysis of Aqueous Humor Outflow Structures with Spectral-Domain Optical Coherence Tomography

PURPOSE To describe morphometric details of the human aqueous humor (AH) outflow microvasculature visualized with 360-degree virtual castings during active AH outflow in cadaver eyes and to compare these structures with corrosion casting studies. METHODS The conventional AH outflow pathways of donor eyes (n = 7) and eyes in vivo (n = 3) were imaged with spectral-domain optical coherence tomography (SD-OCT) and wide-bandwidth superluminescent diode array during active AH outflow. Digital image contrast was adjusted to isolate AH microvasculature, and images were viewed in a 3D viewer. Additional eyes (n = 3) were perfused with mock AH containing fluorescent tracer microspheres to compare microvasculature patterns. RESULTS Observations revealed components of the conventional outflow pathway from Schlemms canal (SC) to the superficial intrascleral venous plexus (ISVP). The superficial ISVP in both our study and corrosion casts were composed of interconnected venules (10-50 μm) forming a hexagonal meshwork. Larger radial arcades (50-100 μm) drained the region nearest SC and converged with larger tortuous vessels (>100 μm). A 360-degree virtual casting closely approximated corrosion casting studies. Tracer studies corroborated our findings. Tracer decorated several larger vessels (50-100 μm) extending posteriorly from the limbus in both raw and contrast-enhanced fluorescence images. Smaller tracer-labeled vessels (30-40 μm) were seen branching between larger vessels and exhibited a similar hexagonal network pattern. CONCLUSIONS SD-OCT is capable of detailed morphometric analysis of the conventional outflow pathway in vivo or ex vivo with details comparable to corrosion casting techniques.

Feasibility of level-set analysis of enface OCT retinal images in diabetic retinopathy.

Pathology segmentation in retinal images of patients with diabetic retinopathy is important to help better understand disease processes. We propose an automated level-set method with Fourier descriptor-based shape priors. A cost function measures the difference between the current and expected output. We applied our method to enface images generated for seven retinal layers and determined correspondence of pathologies between retinal layers. We compared our method to a distance-regularized level set method and show the advantages of using well-defined shape priors. Results obtained allow us to observe pathologies across multiple layers and to obtain metrics that measure the co-localization of pathologies in different layers.

Schlemm’s Canal and Collector Channels as Therapeutic Targets

Intraocular pressure (IOP) is maintained within a normal range from a dynamic balance between aqueous humor formation and drainage. Dysfunctional aqueous drainage results in elevated IOP, which is a causative risk factor for the development and progression of primary open-angle glaucoma (POAG). An understanding of how to lower IOP using microinvasive glaucoma surgery (MIGS) begins with an understanding of the normal anatomy of the structures related to the drainage of aqueous humor and changes in POAG. The major drainage structures for aqueous humor are the conventional or trabecular outflow pathway, which is comprised of the uveal and corneoscleral portions of the trabecular meshwork, the juxtacanalicular connective tissue, Schlemm’s canal, the collector channels, and the aqueous veins. Aqueous humor drains from the anterior chamber through progressively smaller channels of the trabecular meshwork into a circumferencely oriented channel called Schlemm’s canal. From this canal, circuitous channels weave toward the surface of the sclera, ultimately joining the episcleral vasculature which drains into the venous system. Flow through this system is driven by a bulk-flow pressure gradient, and active transport is not involved as neither metabolic poisons nor temperature affects this system to any significant degree. 10–20 % of total aqueous outflow has been reported to leave the normal eye via the uveoscleral pathway which has become a primary target for medical intervention in glaucoma. However, this chapter will only focus on the conventional trabecular outflow pathway.

Enface Thickness Mapping and Reflectance Imaging of Retinal Layers in Diabetic Retinopathy

Purpose To present a method for image segmentation and generation of enface thickness maps and reflectance images of retinal layers in healthy and diabetic retinopathy (DR) subjects. Methods High density spectral domain optical coherence tomography (SDOCT) images were acquired in 10 healthy and 4 DR subjects. Customized image analysis software identified 5 retinal cell layer interfaces and generated thickness maps and reflectance images of the total retina (TR), inner retina (IR), outer retina (OR), and the inner segment ellipsoid (ISe) band. Thickness maps in DR subjects were compared to those of healthy subjects by generating deviation maps which displayed retinal locations with thickness below, within, and above the normal 95% confidence interval. Results In healthy subjects, TR and IR thickness maps displayed the foveal depression and increased thickness in the parafoveal region. OR and ISe thickness maps showed increased thickness at the fovea, consistent with normal retinal anatomy. In DR subjects, thickening and thinning in localized regions were demonstrated on TR, IR, OR, and ISe thickness maps, corresponding to retinal edema and atrophy, respectively. TR and OR reflectance images showed reduced reflectivity in regions of increased thickness. Hard exudates appeared as hyper-reflective spots in IR reflectance images and casted shadows on the deeper OR and ISe reflectance images. The ISe reflectance image clearly showed the presence of focal laser scars. Conclusions Enface thickness mapping and reflectance imaging of retinal layers is a potentially useful method for quantifying the spatial and axial extent of pathologies due to DR.

Comparison of moderate and advanced glaucoma patients in Ghana

Purpose To compare moderate and advanced glaucoma patients in Ghana. Methods A retrospective cross-sectional study of 164 patients with primary open-angle glaucoma (POAG) were separated into moderate and advanced glaucoma groups. Definitions of moderate and advanced POAG were derived from International Geographical and Epidemiologic Ophthalmology criteria and included clinical assessment of optic disc atrophy and Humphrey automated perimetry. Data were collected at the patient’s first visit prior to initiation of therapy. Eligible POAG patients included those ≥30 years old with reliable Humphrey visual field (HVF) results, no past POAG diagnosis, treatment, or evidence of a secondary cause for glaucoma. Main outcome measures included comparisons of intraocular pressure (IOP), cup-to-disk ratio (CDR), best corrected visual acuity (VA), age, Humphrey mean deviation (MD), and pattern standard deviation (PSD). Results Of 164 charts reviewed, 90 (54.9%) advanced and 74 (45.1%) moderate POAG patients were compared. Mean age was 59.36 versus 55.53 years, respectively. Significant differences in IOP, CDR, CDR asymmetry, and HVF results were described. IOP > 30 mmHg was associated with CDR > 0.7 and MD greater than −12 dB in both eyes. Conclusion Significant differences were found between IOP, CDR, MD and PSD values. HVF is predictive of pretreated IOP, CDR, and severity of POAG and it is strongly encouraged as part of the standard glaucoma work up in all Ghanaian patients.

Abnormal Optic Nerves in a Healthy Young Woman

A woman in her 30s was referred for evaluation of bilateral papilledema. She had no specific chief complaint other than intermittent floaters. A review of systems as well as her medical, family, and social history were unremarkable. She was not taking any medications and did not have any allergies. Best-corrected visual acuity was measured 20/25 OD and 20/20 OS. Extraocular movements were intact and pupils were round and reactive with no afferent pupillary defect. Intraocular pressure by applanation was 18 mm Hg OU. Her anterior segment examination was within normal limits. Examination of her fundus revealed the optic nerves seen in Figure 1. The remainder of her posterior segment was unremarkable. Right eye A Left eye B

Comparison of Primary Open Angle Glaucoma Patients in Rural and Urban Ghana

PURPOSE To compare the clinical features of glaucoma patients who present at a rural hospital in North Eastern Ghana and an urban hospital in the capital city of Accra. METHODS This is a multi-center retrospective case series involving records of newly diagnosed glaucoma patients with emphasis on primary open angle glaucoma (POAG). Information collected included basic demographic data, intraocular pressures and optic disc measurements. RESULTS A total of 949 patients (437 rural; 512 urban; 1868 eyes) were included. Rural vs. urban comparisons, respectively: mean age, 53.2 ± 16.3 vs. 54.5 ± 16.4 years; male: female ratio, 3:2 vs. 1:1; POAG, 78.1% vs. 50.6%; POAG suspect, 10.3% vs. 41.9%; IOP, 39.2 ± 7.1 vs. 31.8 ± 7.3 mmHg; bilateral blindness, 34.1% vs. 17.5%; uniocular blindness, 52.2% vs. 32.9%. Females at the rural hospital were twice as likely to present blind in at least one eye (OR 2.04, CI 1.36 - 3.07, p < 0.001). CONCLUSIONS Patients with POAG at the rural hospital present with more advanced disease characteristics.

Assessment of Global and Local Alterations in Retinal Layer Thickness in Ins2 (Akita) Diabetic Mice by Spectral Domain Optical Coherence Tomography

Purpose/Aim The Ins2 (Akita) mouse is a spontaneous diabetic mouse model with a heterozygous mutation in the insulin 2 gene that results in sustained hyperglycemia. The purpose of the study was to assess global and local retinal layer thickness alterations in Akita mice by analysis of spectral domain optical coherence tomography (SD-OCT) images. Materials and Methods SD-OCT imaging was performed in Akita and wild-type mice at 12 and 24 weeks of age. Inner retinal thickness (IRT), outer retinal thickness (ORT), total retinal thickness (TRT), and photoreceptor outer segment length (OSL) were measured. Mean global thickness values were compared between Akita and wild-type mice. Local thickness variations in Akita mice were assessed based on normative values in wild-type mice. Results Akita mice had higher blood glucose levels and lower body weights (p < 0.001). On average, IRT, ORT, and TRT were approximately 2% lower in Akita mice than in wild-type mice (p ≤ 0.02). In Akita mice, the percent difference between retinal areas with thickness below and above normative values for IRT, ORT, and TRT was 22%, 32%, and 38%, respectively. Conclusions These findings support the use of the Akita mouse model to study the retinal neurodegenerative effects of hyperglycemia.

Hemorrhagic Retinopathy after Spondylosis Surgery and Seizure.

PurposeTo report bilateral hemorrhagic retinopathy in an adult female subject after lumbar spinal surgery and seizure. Case ReportA 38-year-old woman presented with bilateral blurry vision and spots in the visual field. The patient had lumbar spondylosis surgery that was complicated by a dural tear with persistent cerebrospinal fluid leak. Visual symptoms started immediately after witnessed seizure-like activity. At presentation, visual acuity was 20/100 and 20/25 in the right and left eye, respectively. Dilated fundus examination demonstrated bilateral hemorrhagic retinopathy with subhyaloid, intraretinal, and subretinal involvement. At 4-month follow-up, visual acuity improved to 20/60 and 20/20 in the right and left eye, respectively. Dilated fundus examination and fundus photography showed resolution of retinal hemorrhages in both eyes. ConclusionsThe first case of bilateral hemorrhagic retinopathy after lumbar spondylosis surgery and witnessed seizure in an adult was reported. Ophthalmic examination may be warranted after episodes of seizure in adults.

Clinical Reasoning: An unusual diagnostic triad

A 44-year-old woman with a history of hypothyroidism taking daily levothyroxine was admitted to an outside hospital with subacute cognitive decline. Her symptoms had started 3 weeks previously with headache, sore neck, and upper respiratory symptoms for which she sought care at a local emergency room. She did not complain of confusion or demonstrate signs of cognitive decline at that time and was discharged home with a prescription for antibiotics. A few days later, she was hospitalized after appearing disoriented, exhibiting signs of confusion, responding slowly, and running into things at work.