A. Shakoor

A Method for Chorioretinal Oxygen Tension Measurement

Purpose: To report an optical imaging system that was developed to measure oxygen tension (pO2) in the chorioretinal vasculatures. The feasibility of the system for the measurement of changes in pO2 separately in the retinal and choroidal vasculatures was established in rat eyes by varying the fraction of inspired oxygen and inhibiting nitric oxide activity. Methods: Our optical section phosphorescence imaging system was modified to provide quantitative measurements of pO2 separately in the retinal and choroidal vasculatures. A narrow laser line was projected at an angle on the retina after intravenous injection of an oxygen-sensitive probe (Pd-porphyrin), and phosphorescence emission was imaged. A frequency-domain approach allowed measurements of the phosphorescence lifetime by varying the phase relationship between the modulated excitation laser light and sensitivity of the imaging camera. Chorioretinal pO2 was measured while varying the fraction of inspired oxygen and during intravenous infusion of Nω-nitro-L-arginine (Nω-NLA), a nonselective nitric oxide synthase inhibitor. Results: The systemic arterial pO2 varied according to the fraction of inspired oxygen. The pO2 in the retinal and choroidal vasculatures increased as the fraction of inspired oxygen was increased. Compared with baseline, choroidal pO2 decreased during infusion of Nω-NLA, whereas the pO2 in the retinal vasculatures remained relatively unchanged. The choroidal pO2 decreased markedly with each incremental increase in Nω-NLA infusion rate, in the range 1–6 mg/min, and there was no additional change in the choroidal pO2 at Nω-NLA infusion rates above 6 mg/min. Conclusions: An optical method combining pO2 phosphorescence imaging with chorioretinal optical sectioning was established that can potentially be applied for better understanding of retinal and choroidal oxygen dynamics in physiologic and pathologic states.

Nerve fiber layer thickness in glaucoma patients with asymmetric hemifield visual field loss.

PurposeTo investigate the presence of retinal nerve fiber layer (RNFL) thinning and determine the relationship between RNFL thickness and visual field sensitivity loss in glaucoma patients with asymmetric hemifield visual field loss. Patients and MethodsThirty glaucoma patients with asymmetric hemifield visual field loss and 30 normal control subjects were included in the study. RNFL thickness was measured by optical coherence tomography and visual field sensitivity was measured by automated perimetry. Glaucoma patients with advanced visual field loss restricted to 1 hemifield and early or absent glaucomatous field loss in the other hemifield on the basis of the visual field data were included. Visual field sensitivity and mean deviation (MD) were averaged separately in each of the 2 hemifields. The hemifields in each eye were categorized as early (MD≥−6 dB) and advanced (MD<−6 dB) glaucomatous hemifields. ResultsRNFL thickness measurements in corresponding (eg, superior peripapillary quadrant with inferior hemifield) advanced glaucomatous hemifields (59±16 μm) were significantly (P<0.001) lower than in corresponding early glaucomatous hemifields (90±25 μm). The mean RNFL thickness in corresponding advanced and early glaucomatous hemifields were significantly lower than in normal control subjects (P<0.0001). On the basis of the normative database supplied by optical coherence tomography software, 100% and 43% of eyes had abnormal RNFL thickness in corresponding advanced and early glaucomatous hemifields, respectively. A linear correlation was found between RNFL thickness and MD in the early (r=0.6; P<0.001) and advanced (r=0.5; P=0.007) glaucomatous hemifields. ConclusionsRNFL thinning was present in corresponding hemifields of glaucomatous eyes with minimal visual field defect and correlated with visual field sensitivity loss. Measurement of RNFL thickness has potential for detection of early nerve fiber loss owing to glaucoma.

Chorioretinal Vascular Oxygen Tension in Spontaneously Breathing Anesthetized Rats

Purpose: To establish baseline and variability of oxygen tension (PO2) measurements in the choroid, retinal arteries, capillaries, and veins of spontaneously breathing anesthetized rats and determine the effect of a moderate surgical procedure on the chorioretinal PO2. Methods: Our previously established optical section phosphorescence imaging technique was utilized to measure PO2 in the chorioretinal vasculatures. Imaging was performed in 29 spontaneously breathing rats under ketamine/xylazine anesthesia. In 7 rats, blood was drawn using a surgically implanted femoral arterial catheter and analyzed to determine the systemic arterial PO2. The PO2 measurements in 22 rats without surgery (group 1) and 7 surgically instrumented rats (group 2) were statistically compared. The intrasubject variability was calculated by the average standard deviation (SD) of repeated measurements. Results: The average systemic arterial PO2 was 52 ± 7 mm Hg (mean ± SD) in group 2. In group 1, the average PO2 measurements in the choroid, retinal arteries, capillaries, and veins were 50 ± 11, 40 ± 5, 39 ± 6, and 30 ± 5 mm Hg, respectively. No statistically significant PO2 differences in any of the chorioretinal vasculatures were found between the two groups (p > 0.4). The intrasubject variability was 3 mm Hg in the choroid, retinal arteries, capillaries, and veins. Conclusions: Chorioretinal PO2 measurements in spontaneously breathing anesthetized rats have a relatively low variability, indicating that PO2 changes due to various physiological alterations can be reliably assessed.

Noninvasive Assessment of Chorioretinal Oxygenation Changes in Experimental Carotid Occlusion

Purpose: To demonstrate the capability of our optical imaging system to assess oxygenation changes in chorioretinal vasculatures due to experimentally induced carotid occlusion. Methods: Chorioretinal oxygenation was assessed by projecting a narrow laser line at an angle on the retina after intravenous injection of an oxygen sensitive probe and imaging phosphorescence emission. Optical section phosphorescence imaging was performed in rats, under steady-state conditions and during unilateral occlusion of the common carotid artery. Phosphorescence intensity was measured in the retinal vein, artery, capillaries, and choroid vascular areas. Oxygenation was defined as the inverse of phosphorescence intensity. Oxygenation changes in the four vascular areas were determined relative to initial preocclusion oxygenation values and compared to measured changes under steady-state conditions. Results: Under steady-state conditions, phosphorescence intensity in chorioretinal vasculatures remained constant, displaying a change of ≤8% over time. At 12 ± 5 s from initiation of occlusion, oxygenation decreased in the retinal venous, arterial, capillary, and choroidal circulations by −41 ±19%, −10 ± 5%, −20 ± 18%, −10 ± 5%, respectively (p ≤ 0.05; n = 6). At 30 ± 10 s from initiation of occlusion, oxygenation change in the retinal vein, artery, capillaries, and choroid was −9 ± 12%, −2 ± 4%, −11 ± 21%, −1 ± 8%, respectively, and not statistically different as compared to steady-state oxygenation changes (p ≥ 0.3; n = 6). Conclusions: Optical section phosphorescence imaging technique can be used to assess intravascular oxygenation changes and may be a valuable tool for studying disease-related oxygen dynamics in the chorioretinal vasculatures.

Macular thickness mapping in exudative age-related macular degeneration.

Purpose: To report the feasibility of retinal thickness mapping for evaluating thickness differences in retinal areas with and without leakage shown by fluorescein angiography for patients who have age-related macular degeneration with choroidal neovascularization. Methods: A custom-built version of the retinal thickness analyzer was used for thickness mapping. Retinal thickness was defined as the separation between vitreoretinal and pigment epithelium–choroid interfaces. Imaging was performed in 1 eye of 10 patients with the clinical diagnoses of age-related macular degeneration and choroidal neovascularization. Patients either had never undergone photodynamic therapy at the time of measurement (untreated) or had received one or more photodynamic therapy treatments (treated). Average retinal thicknesses in selected areas with and without the presence of leakage shown by fluorescein angiography were calculated and compared statistically. Results: Retinal thickness (mean ± SD) in areas with leakage (315 ± 54 &mgr;m) was significantly greater than that in areas without leakage (280 ± 28 &mgr;m) (P = 0.03). In untreated patients, areas with leakage (345 ± 45 &mgr;m) were significantly thicker than areas without leakage (289 ± 23 &mgr;m) (P = 0.02). In treated patients, retinal thickness in areas with leakage (271 ± 33 &mgr;m) and without leakage (267 ± 34 &mgr;m) was similar. Conclusion: Retinal thickness mapping may prove to be useful as an adjunct to fluorescein angiography to monitor choroidal neovascularization and its treatment.