Raghu C. Mudumbai

Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography–Based Microangiography

Purpose To investigate the vascular microcirculation changes in the retinal nerve fiber layer (RNFL) in normal, glaucoma suspect, and open-angle glaucoma (OAG) groups using optical coherence tomography–based microangiography (OMAG). Methods One eye from each subject was scanned with a Cirrus HD-OCT 5000–based OMAG prototype system montage scanning protocol centered at the optic nerve head (ONH). Blood flow signals were extracted using OMAG algorithm. Retinal nerve fiber layer vascular microcirculation was measured by calculating the blood flux index and vessel area density within a 1.2-mm width annulus centered at the ONH with exclusion of big retinal vessels. One-way ANOVA were performed to analyze the RNFL microcirculation among groups. Linear-regression models were constructed to analyze the correlation between RNFL microcirculation and clinical parameters. Discrimination capabilities of the flow metrics were assessed with the area under the receiver operating characteristic curve (AROC). Results Twenty normal, 26 glaucoma suspect, and 42 OAG subjects were enrolled. Eyes from OAG subjects and glaucoma suspects showed significantly lower blood flux index compared with normal eyes (P ≤ 0.0015). Retinal nerve fiber layer blood flow metrics showed significant correlations with visual field indices and structural changes in glaucomatous eyes (P ≤ 0.0123). Similar discrimination capability of blood flux index compared with RNFL thickness was found in both disease groups. Conclusions Peripapillary RNFL vascular microcirculation measured as blood flux index by OMAG showed significant differences among OAG, glaucoma suspect, and normal controls and was significantly correlated with functional and structural defects. Retinal nerve fiber layer microcirculation measurement using OMAG may help physicians monitor glaucoma.

Optic nerve head perfusion in normal eyes and eyes with glaucoma using optical coherence tomography-based microangiography.

BACKGROUND To investigate the differences of perfusion in the optic nerve head (ONH) between normal and glaucomatous eyes using optical microangiography (OMAG) based optical coherence tomography (OCT) angiography technique. METHODS One eye from each subject was scanned with a 68 kHz Cirrus 5000 HD-OCT-based OMAG prototype system centered at the ONH (Carl Zeiss Meditec Inc, Dublin, CA, USA). Microvascular images were generated from the OMAG dataset by detecting the differences in OCT signal between consecutive B-scans. The pre-laminar layer (preLC) was isolated by a semi-automatic segmentation program. En face OMAG images for preLC were generated using signals with highest blood flow signal intensity. ONH perfusion was quantified as flux, vessel area density, and normalized flux within the ONH. Standard t-tests were performed to analyze the ONH perfusion differences between normal and glaucomatous eyes. Linear regression models were constructed to analyze the correlation between ONH perfusion and other clinical measurements. RESULTS Twenty normal and 21 glaucoma subjects were enrolled. Glaucomatous eyes had significantly lower ONH perfusion in preLC in all three perfusion metrics compared to normal eyes (P≤0.0003). Significant correlations between ONH perfusion and disease severity as well as structural changes were detected in glaucomatous eyes (P≤0.012). CONCLUSIONS ONH perfusion detected by OMAG showed significant differences between glaucoma and normal controls and was significantly correlated with disease severity and structural defects in glaucomatous eyes. ONH perfusion measurement using OMAG may provide useful information for detection and monitoring of glaucoma.

Human orbital sympathetic nerve pathways

Purpose: To determine pathways of sympathetic nerves from the orbital apex to the eyelids in human cadaver tissue using immunohistochemistry. Methods: Human cadaver orbit tissue was sectioned and immunolabeled with a monoclonal antityrosine hydroxylase antibody. Results: In the orbital apex, the nasociliary, frontal, lacrimal, and maxillary branches of the trigeminal nerve demonstrated intense staining upon entering the orbit. Immunoreactive axons from the nasociliary and frontal nerves were observed to join the extraocular motor nerves in the posterior orbit. A plexus of immunolabeled nerves was observed to accompany the ophthalmic artery as it entered the orbital apex. The ophthalmic artery and its branches throughout the orbit demonstrated staining of nerve fibers in the peripheral muscularis. The nasociliary nerve contributed sympathetic branches to the ciliary ganglion. Nerves passing through the ciliary ganglion and a few ganglion cell bodies demonstrated mild to moderate tyrosine hydroxylase reactivity. Axons within the short and long ciliary nerves demonstrated strong tyrosine hydroxylase reactivity and were observed to enter the posterior sclera and the suprachoroidal space. The lacrimal gland demonstrated mild pericapillary staining and occasional stromal nerve fibers reactive to the antityrosine hydroxylase antibody. Müller muscle and the inferior tarsal muscle possessed a strong tyrosine hydroxylase-reactive nerve supply that appeared to originate from the anterior terminal branches of the nasociliary and lacrimal nerves. Conclusions: Sympathetic nerves enter the orbit via the first and second divisions of the trigeminal nerve and a plexus of nerves surrounding the ophthalmic artery. Extraocular motor nerves receive a sympathetic nerve supply from the sensory nerves in the posterior orbit. Some ciliary ganglion cell bodies demonstrated tyrosine hydroxylase-like reactivity, suggesting a sympathetic modulatory role for the ciliary ganglion. Sympathetics innervate ocular structures via the posterior ciliary nerves. Sympathetic axons travel anteriorly in the orbit via the nasociliary and lacrimal nerves to innervate the sympathetic eyelid muscles. Sympathetic nerves also travel with the frontal branch of the ophthalmic nerve to innervate the forehead skin. The ophthalmic artery and all of its branches contain a perivascular sympathetic nerve supply that may be involved in regulation of blood flow to ocular and orbital structures.

Combined exfoliation and pigment dispersion paradigm of an overlap syndrome

OBJECTIVE To describe a series of patients with combined pigment dispersion syndrome (PDS) and exfoliation syndrome (XFS) and to introduce a concept, the overlap syndrome, to aid in assessing multiple risk factors for glaucomatous damage. DESIGN Clinic-based, cross-sectional study. SETTING New York Eye and Ear Infirmary. PARTICIPANTS Twenty-six patients identified from the glaucoma database as having combined pigment dispersion syndrome-glaucoma and exfoliation syndrome-glaucoma. MAIN OUTCOME MEASURES Quantification of patients with both pigment dispersion syndrome-glaucoma (PDS/PG) and exfoliation syndrome-glaucoma (XFS/XFG) and its clinical implications. RESULTS Among the 26 patients (all white) having both XFS/XFG and PDS/PG, the average age was 64.3 +/- 9.8 years and 19 of 26 were men. All patients had bilateral PDS/PG. Bilateral XFS/XFG was present in 9 of 26 patients and, of the 17 patients with unilateral involvement, the left eye was affected in 13. CONCLUSIONS Both XFS and PDS are common. Middle-aged patients with known PDS/PG should be suspected of having the onset of XFS if one eye escapes intraocular pressure control. Patients with unilateral XFG at presentation may also have signs of PDS/PG, often remitted. We define the term overlap syndrome to describe the sequential appearance over time of two or more risk factors for glaucomatous damage. The appearance of a new risk factor in a patient whose condition has been stable can alter the course and prognosis of the disease. This concept should prove useful in dealing with secondary and normal-tension glaucomas.

Glaucoma in Patients With Ocular Chemical Burns

PURPOSE To examine the development and management of glaucoma in patients with ocular chemical burns. DESIGN Retrospective, observational case series. METHODS setting: University of Washington Eye Clinics. patient population: Twenty-nine eyes (18 patients) with ocular chemical burns seen between 1997 and 2010 with a minimum of 3 months of follow-up. observation procedure: Eyes were graded using the Roper-Hall scale. main outcome measures: Long-term use of glaucoma medications (3 months or more) and need for glaucoma surgery. RESULTS The mean age was 45 ± 17 years, with a mean follow-up of 75 ± 47 months (median, 66 months). Roper-Hall grade III or IV eyes (n = 20) had significantly higher intraocular pressure at presentation (35.9 vs 16.4 mm Hg; P = .001) and over follow-up were more likely to require long-term glaucoma medications (P = .003) or to undergo glaucoma surgery (P = .016) than Roper-Hall grade I or II eyes. Thirteen eyes (12 Roper-Hall grade III or IV) underwent glaucoma surgery. Eight eyes underwent glaucoma tube implant surgery; 4 required at least 1 revision. Seven eyes underwent diode laser cyclophotocoagulation; 4 required repeat treatment. Most (89%) eyes had controlled intraocular pressure at the last follow-up. However, 76% of eyes with visual acuity of 20/200 or worse at initial evaluation did not have improved vision at the last follow-up. CONCLUSIONS Eyes with Roper-Hall grade III or IV ocular chemical burns were more likely to have glaucoma and to require surgery for it. Outcomes of glaucoma management generally were good, although tube implant surgeries often had complications requiring revision.

Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Eyes With Glaucoma and Single-Hemifield Visual Field Loss

Importance Understanding the differences in vascular microcirculation of the peripapillary retinal nerve fiber layer (RNFL) between the hemispheres in eyes with glaucoma with single-hemifield visual field (VF) defects may provide insight into the pathophysiology of glaucoma. Objective To investigate the changes in the microcirculation of the peripapillary RNFL of eyes with glaucoma by using optical microangiography. Design, Setting, and Participants Eyes with glaucoma and single-hemifield VF defect and normal eyes underwent scanning using an optical microangiography system covering a 6.7 × 6.7-mm2 area centered at the optic nerve head. The RNFL microcirculation was measured within an annulus region centered at the optic nerve head divided into superior and inferior hemispheres. Blood flux index (the mean flow signal intensity in the vessels) and vessel area density (the percentage of the detected vessels in the annulus) were measured. Main Outcomes and Measures Differences in microcirculation between the hemispheres in eyes with glaucoma and normal eyes and correlations among blood flow metrics, VF thresholds, and clinical optical coherence tomography structural measurements were assessed. Results Twenty-one eyes from 21 patients with glaucoma (7 men and 14 women; mean [SD] age, 63.7 [9.9] years) and 20 eyes from 20 healthy control individuals (9 men and 11 women; mean [SD] age, 68.3 [10.7] years) were studied. In eyes with glaucoma, the abnormal hemisphere showed a thinner RNFL (mean [SE] difference, 23.5 [4.5] &mgr;m; 95% CI, 15.1-32.0 µm; P < .001), lower RNFL blood flux index (mean [SE] difference, 0.04 [0.01]; 95% CI, 0.02-0.05; P < .001), and less vessel area density (mean [SE] difference, 0.08% [0.02%]; 95% CI, 0.05%-0.10%; P < .001) than did the normal hemisphere. Compared with normal eyes, reduced RNFL microcirculation was found in the normal hemisphere of eyes with glaucoma, measured by mean [SE] differences in blood flux index (0.06 [0.01]; 95% CI, 0.04-0.09; P < .001) and vessel area density (0.04% [0.02%]; 95% CI, 0.02%-0.08%; P = .003) but not in RNFL thickness (3.4 [4.7] &mgr;m; 95% CI, −6.2 to 12.9 µm; P = .48). Strong correlations were found between the blood flux index and VF mean deviation (Spearman &rgr; = 0.44; P = .045) and RNFL thickness (Spearman &rgr; = 0.65; P = .001) in the normal hemisphere of the eye with glaucoma. Conclusions and Relevance Reduced RNFL microcirculation was detected in the normal hemisphere of eyes with glaucoma, with strong correspondence with VF loss and RNFL thinning. Although the results suggest that vascular dysfunction precedes structural changes seen in glaucoma, longitudinal studies would be needed to confirm this finding.

Clinical update on normal tension glaucoma.

ABSTRACT Normal tension glaucoma (NTG) is a common form of open-angle glaucoma that can lead to significant visual morbidity. There has been considerable debate as to whether NTG fits within the spectrum of primary open-angle glaucoma (POAG). The relative roles of intraocular pressure and pressure-independent factors in this disease have also been debated. This review provides an extensive analysis of key clinical features, differential diagnoses, and potential pathophysiologic mechanisms, both intraocular and systemic, of NTG. Findings of major clinical trials and evidence-based guidelines for management are also reviewed.

Repeatability and reproducibility of optic nerve head perfusion measurements using optical coherence tomography angiography

Abstract. Optical coherence tomography angiography (OCTA) has increasingly become a clinically useful technique in ophthalmic imaging. We evaluate the repeatability and reproducibility of blood perfusion in the optic nerve head (ONH) measured using optical microangiography (OMAG)-based OCTA. Ten eyes from 10 healthy volunteers are recruited and scanned three times with a 68-kHz Cirrus HD-OCT 5000-based OMAG prototype system (Carl Zeiss Meditec Inc., Dublin, California) centered at the ONH involving two separate visits within six weeks. Vascular images are generated with OMAG processing by detecting the differences in OCT signals between consecutive B-scans acquired at the same retina location. ONH perfusion is quantified as flux, vessel area density, and normalized flux within the ONH for the prelaminar, lamina cribrosa, and the full ONH. Coefficient of variation (CV) and intraclass correlation coefficient (ICC) are used to evaluate intravisit and intervisit repeatability, and interobserver reproducibility. ONH perfusion measurements show high repeatability [CV≤3.7% (intravisit) and ≤5.2% (intervisit)] and interobserver reproducibility (ICC≤0.966) in all three layers by three metrics. OCTA provides a noninvasive method to visualize and quantify ONH perfusion in human eyes with excellent repeatability and reproducibility, which may add additional insight into ONH perfusion in clinical practice.

Evaluation of bilateral central retinal artery occlusions with optical coherence tomography-based microangiography: a case report.

BackgroundWe report a case of bilateral central retinal artery occlusion and the evaluation of retinal vasculature and capillaries by using optical coherence tomography angiography.Case presentationA 75-year-old white man presented with central retinal artery occlusion in one eye and underwent a carotid angioplasty. Upon discontinuing anticoagulant, he had a subsequent central retinal artery occlusion in the other eye. Optical coherence tomography angiography images were obtained to compare the retinal microvasculature in both eyes.ConclusionsAtrophy of the involved retina continues for several weeks after central retinal artery occlusion but the loss of retinal capillaries is immediate and stable over time. The presence of cilioretinal arteries that perfuse the central macula can prevent profound vision loss.

Prevalence of self-reported early glaucoma eye drop bottle exhaustion and associated risk factors: a patient survey

BackgroundOne barrier to patient adherence with chronic topical glaucoma treatment is an inadequate amount of medication available between prescription refills. We examined the self-reported prevalence of early exhaustion of glaucoma eye drops prior to a scheduled refill, and associated risk factors.MethodsThis cross-sectional survey was performed at a University-based clinical practice. Glaucoma patients at the University of Washington who were experienced with eye drop application and were on a steady regimen of self-administered glaucoma drops in both eyes took a survey at the time of clinic examination. The main outcome measure was self-reported early eye drop bottle exhaustion.Results236 patients were eligible and chose to participate. In general, patients included were relatively healthy (mean 2.3 comorbid medical conditions). Sixty patients (25.4%) reported any problem with early exhaustion of eye drop bottles, and this was associated with visual acuity ≤ 20/70 in the better eye (P = .049). Twelve patients (5.1%) reported that they “often” (5–7 times per year), “usually” (8–11 times per year) or “always” ran out of eye drops prior to a scheduled refill. Patients affected by this higher level (≥5 times yearly) of eye drop bottle exhaustion were more likely to have poor visual acuity in their worse eye ≤ 20/70 (P = .015) and had significantly lower worse-eye logMAR (P = .043).ConclusionsSelf-reported early glaucoma bottle exhaustion regularly affected 5% of patients in our population and 25% reported early exhaustion at least once; the main risk factor was poor vision in at least one eye. These results may not be generalizable to a broad patient population, or to those inexperienced with eye drop self-administration. However, this pilot study compels further evaluation and consideration of early eye drop bottle exhaustion in glaucoma patients.