Computerized stereochronoscopy and alternation flicker to detect optic nerve head contour change.

PURPOSE/BACKGROUND: Stereochronoscopy, a technique previously explored but abandoned for glaucoma diagnosis, viewed optic nerve images acquired at separate points in time as if a stereo pair. Prior efforts to exploit this technique were impaired by a lack of superimposability for sequential optic nerve images. We investigated computerized registration techniques for aligning sequential, monoscopic optic disc images to facilitate sensitive detection of optic nerve head contour changes in glaucoma. DESIGN: Algorithm and software development. Comparisons with standard techniques. MATERIALS: Existing patient records from the Glaucoma Service, Scheie Eye Institute, University of Pennsylvania. METHODS: Two sets of optic disc photographs, separated in time by 1 to 18 years, of 25 eyes with and without glaucomatous optic disc progression were digitized. We developed custom software for accurate image alignment. Change in disc morphology was then judged by digital stereochronoscopy and user-controlled alternation flicker of superimposed, time-separated images on a computer monitor. Comparisons were made with standard stereoscopic comparison. MAIN OUTCOME MEASURE: Identification of change or no change in optic nerve head contour for images acquired at separate points in time. RESULTS: Image processing and registration permits accurate alignment of optic disc photographs. Alternation flicker of superimposed, sequential images facilitates image comparison and detection of change as indicated by change in vessel position, color, and other cues for contour change. A high concordance was found between standard stereoscopic comparison and alternation flicker. In several cases, reinspection of stereo comparison led to a revised judgment on the basis of disc changes rendered more obvious with alternation flicker. Digital stereochronoscopy was less concordant with standard techniques. CONCLUSIONS: Digital image processing techniques and alternation flicker provide a simple, sensitive, software-based method for detecting glaucomatous optic disc change.

A false-positive Seidel test after Ahmed valve insertion.

An 80-year-old monocular man with long-standing primary open angle glaucoma underwent successful filtering surgery in his sighted right eye in 1980. He subsequently developed a cataract and had an uncomplicated clear cornea phacoemulsification with posterior chamber intraocular lens in 1996. Post-operatively, the filtration bleb remained very avascular but shallowed; the intraocular pressure increased and remained uncontrolled despite maximally tolerated medical therapy. His vision improved to 6/7.5 and automated perimetry revealed a less than 5 degrees small central island of vision. His left eye was phthisical with no light perception.

The effect of nimodipine, a centrally active calcium antagonist, on visual function and mascular blood flow in patients with normal-tension glaucoma and control subjects.

PURPOSE: This study was performed to evaluate the effect of nimodipine, a centrally active calcium channel antagonist on automated Humphrey visual fields, Farnsworth-Munsell 100 (FM-100) hue color vision testing, and macular blood flow (blue field entoptic simulation technique) in patients with normal-tension glaucoma (NTG) and control subjects. METHODS: Thirteen patients with NTG and thirteen age- and sex-matched control subjects were studied in a prospective, placebo-controlled, double-masked, crossover protocol. On each of the two study dates, testing was performed at baseline and 90 minutes after administration of either two 30-mg nimodipine capsules or two identical appearing placebo capsules. Blood pressure and pulse were monitored throughout the study. RESULTS: Nimodipine administration resulted in a performance corrected improvement in Humphrey visual field mean deviation (patients with NTG and control subjects), corrected pattern standard deviation (patients with NTG), and macular sensitivity (the average of the foveal threshold and the four most central points of the visual field; patients with NTG). The FM-100 hue error scores significantly decreased after administration of nimodipine in patients with NTG and control subjects compared with baseline. There were no significant differences in baseline leukocyte velocity or density between patients with NTG and control subjects; no significant changes in leukocyte velocity or density were noted after administration of nimodipine in either group. CONCLUSION: Nimodipine caused a significant performance corrected improvement in visual field testing and a significant improvement in color vision. Nimodipine did not alter macular hemodynamics as measured using the blue field entoptic simulation technique, although results were hampered by high variability, particularly in the leukocyte density measurements.

Fenoldopam, a selective dopamine-1 receptor agonist, raises intraocular pressure in males with normal intraocular pressure.

Recent studies have suggested that intravenous infusion of fenoldopam, a selective dopamine-1 receptor agonist, elevates intraocular pressure (IOP) in man. This study evaluated the effect of intravenous fenoldopam on IOP, aqueous humor outflow facility and gonioscopy in 12 healthy human subjects. Three doses (0.2, 0.5 and 1.0 microg/kg/min) were infused for 120 minutes in a double masked, placebo controlled, four-way crossover design. IOP was measured every 20 minutes in the supine position and every 40 minutes while sitting during the drug and placebo infusions. Tonography and gonioscopy were performed at baseline and after 120 minutes of infusion. Compared to placebo, IOP increased by 3.5 mm Hg (32%) for the lowest dose, 5.8 mm Hg (46%) for the intermediate dose, and 6.9 mm Hg (55%) for the highest dose (p<0.05 for all three doses). IOP returned to baseline within 30 minutes of stopping the infusion. The outflow facility decreased from baseline by 26% after 120 minutes of infusion for all drug doses. In contrast, outflow facility increased from baseline by 11% during placebo infusion. Compared to placebo, the fenoldopam induced changes in outflow were statistically significant (p<0.05). There was no change in the gonioscopic appearance of the anterior chamber angle during the infusion. This study shows that systemic administration of a selective dopamine-1 receptor agonist causes a significant dose-dependent increase in IOP that can be explained in part by diminished outflow facility. These results support a role for the dopamine-1 receptor in the modulation of IOP in general and suggest modulation of aqueous humor outflow by dopaminergic receptors.

Nimodipine, a centrally active calcium antagonist, exerts a beneficial effect on contrast sensitivity in patients with normal-tension glaucoma and in control subjects.

BACKGROUND/PURPOSE: The use of calcium antagonists in patients with normal-tension glaucoma (NTG) currently is under investigation. The aim of this study is to evaluate the effect of an acute dose of oral nimodipine, a centrally active calcium antagonist, on spatial contrast sensitivity in patients with NTG and in age-matched control subjects. METHODS: Spatial contrast sensitivity was measured using the Pelli-Robson and the Vistech 6000 charts in 14 patients with NTG and in 17 control subjects. Testing was performed at baseline and at two subsequent sessions. Measurements were recorded 2 hours after oral administration of either nimodipine or placebo in a randomized, double-masked manner. Data were analyzed using unpaired, two-tailed Student's t test for between-group comparisons and repeated measures analysis of variance for within-group comparisons. RESULTS: Using the Pelli-Robson charts, baseline contrast sensitivity was significantly lower in patients with NTG compared with control subjects (P < 0.05, unpaired Student's t test). There was a significant increase in log contrast sensitivity after administration of nimodipine compared with baseline and placebo in patients with NTG (baseline, 1.39 +/- 0.38; placebo, 1.41 +/- 0.40; nimodipine, 1.51 +/- 0.39) and in control subjects (baseline, 1.62 +/- 0.11; placebo, 1.64 +/- 0.10; nimodipine, 1.81 +/- 0.14) (P < 0.05, repeated measures analysis of variance). A similar trend was observed using the Vistech charts. CONCLUSION: These results suggest that central visual function as measured by Pelli-Robson and Vistech contrast sensitivity is impaired in eyes with NTG. An acute, oral administration of nimodipine, a calcium antagonist, improved contrast sensitivity in patients with NTG and in control subjects. The mechanism of this improvement is not fully understood. Further studies are needed to evaluate the effect of long-term administration in glaucoma.

The use of subconjunctivally administered tissue plasminogen activator after trabeculectomy.

Blockage of aqueous flow in the early postoperative period can be devastating to the success of trabeculectomy. We used tissue plasminogen activator (tPA) subconjunctivally in an attempt to release a trabeculectomy flap that appeared to be adherent to its scleral bed. No change was noted 90 minutes after injection, but a highly elevated bleb was present on the first postoperative day. Subconjunctivally administered tPA may be useful in releasing the fibrin "glue" in cases with adherent trabeculectomy flaps.

Digoxin toxicity. Recognizing the varied visual presentations.

We report three cases of digoxin toxicity presenting with decreased visual acuity, unaccompanied by the classic visual symptom of xanthopsia. Visual function improved and symptoms diminished upon lowering of blood digoxin level. Electroretinographic (ERG) abnormalities in the first case were suggestive of a cone deficit, which supports recent electrodiagnostic and labeled tracer studies implicating retinal dysfunction in the pathogenesis of digoxin toxicity. The second patient presented with visual symptoms exclusively. Evaluation of the third case was hampered by advanced retinitis pigmentosa and the presentation was complicated by a syncopal episode. Digoxin toxicity is a potentially life-threatening condition. Ophthalmologists and neurologists may be the first physicians consulted. It must be considered in the differential diagnosis in patients with otherwise unexplained visual loss.

Vernier thresholds and alignment bias in control, suspect, and glaucomatous eyes.

Detection of vernier offsets requires integration of spatial information from many retinal receptive fields. It was postulated that diminution of the number of ganglion cells in glaucoma may diminish the spatial sampling grain, compromise these integrative processes, and raise vernier thresholds. To test this hypothesis, vernier thresholds were measured in 45 patients with primary open-angle glaucoma (POAG), 45 age-matched glaucoma suspects, and 45 age-matched controls. Alignment bias was measured in 43 subjects from each diagnostic group. Measurements were also obtained in an additional 29 control subjects to evaluate the effect of age on vernier thresholds. All subjects had acuities of 6/7.5 or better. Vernier thresholds were significantly greater in glaucomatous eyes and suspect eyes than in control eyes (p = 0.0002). Mean thresholds were increased by 64% in glaucomatous eyes and 47% in suspect eyes; however, there was significant overlap between the groups. A subgroup of 15 eyes with early glaucomatous damage without localized visual field defects also had vernier thresholds significantly greater than control eyes (p = 0.02). The variances of the alignment biases were significantly greater in the glaucomatous and suspect eyes than in controls eyes (p < 0.05). Our results demonstrate that significant deficits of vernier detection can be demonstrated in some glaucomatous eyes, even in the absence of defects on automated perimetry. Because of the overlap between diagnostic groups, measurement of vernier thresholds cannot be used to distinguish POAG from controls. However, elevation of vernier thresholds may serve as a marker for the early diffuse central dysfunction that occurs in some eyes with glaucoma. The significance of these findings in terms of the mechanisms of glaucomatous damage is discussed.

A technique for accurate application of pilocarpine gel.

Pilocarpine hydrochloride 4% gel can be accurately administered by squeezing a one-half inch ribbon of gel onto the tube tip and then touching the premeasured dose to the conjunctiva.

Momentary fluctuations of intraocular pressure in normal and glaucomatous eyes.

To examine the range of momentary fluctuations of intraocular pressure caused by vascular pulsations in 42 glaucomatous and 18 normal eyes, we obtained consecutive intraocular pressure measurements at hourly intervals with a noncontact air tonometer. Glaucomatous eyes had a significantly (P less than .001) greater range of intraocular pressure measurements on consecutive readings than normal eyes (4.4 +/- 1.4 mm Hg vs 2.7 +/- 0.7 mm Hg). The frequency of consecutive intraocular pressure readings exceeding a spread of 4 mm Hg was significantly increased in glaucomatous eyes. The range of intraocular pressure measurements was greater even in those glaucomatous eyes with mean intraocular pressures within the normal range. There was a positive correlation between mean intraocular pressure and mean range in glaucomatous eyes, but not in normal eyes. In both glaucomatous and normal eyes, there was no significant correlation between age and mean range.