Jody R. Piltz-Seymour

Optic nerve blood flow is diminished in eyes of primary open-angle glaucoma suspects.

PURPOSE The purpose of this study was to evaluate optic nerve blood flow in primary open-angle glaucoma suspect eyes with normal automated visual fields, in an attempt to elucidate how early in the glaucomatous disease process changes in optic nerve blood flow become apparent. METHODS Twenty-one eyes (21 patients) suspected of having primary open-angle glaucoma were studied prospectively and compared with a previously reported cohort of 22 eyes (22 patients) with primary open-angle glaucoma and 15 eyes (15 subjects) of age-matched controls. Primary open-angle glaucoma suspect eyes had untreated intraocular pressure greater than 21 mm Hg and normal visual fields using Humphrey program 24-2 or 30-2 with a full threshold strategy. Laser Doppler flowmetry was used to measure optic nerve head blood velocity, volume, and flow at four quadrants in the optic nerve, in the cup, and in the foveola of one eye of each patient. The mean flow from the superotemporal rim, inferotemporal rim, and cup was calculated (Flow(3)) and identified as the main outcome measure. Measurements from primary open-angle glaucoma suspect eyes were compared with corresponding measurements from controls and eyes with primary open-angle glaucoma; a Student t test was employed with a Bonferroni corrected P value of.025 to account for comparisons of primary open-angle glaucoma suspects both to controls and to eyes with primary open-angle glaucoma. RESULTS Compared with controls, Flow(3) was 24% lower in primary open-angle glaucoma suspect eyes (P <.0003). In primary open-angle glaucoma suspect eyes, flow was 16% lower in the superotemporal rim (P <.007), 35% lower in the cup (P <.007), and 22% lower in the inferotemporal neuroretinal rim (P <.029) compared with controls. No significant difference between primary open-angle glaucoma suspect and control eyes was seen in the inferonasal rim, superonasal rim, or foveola. No significant difference was detected at any location between primary open-angle glaucoma suspect eyes and eyes with primary open-angle glaucoma. CONCLUSIONS Laser Doppler flowmetry detected circulatory abnormalities in primary open-angle glaucoma suspects who did not have any manifest visual field defect. Decreases in flow in glaucoma suspects were similar in magnitude to those of subjects with primary open-angle glaucoma. These data suggest that impaired optic nerve blood flow develops early in the glaucomatous process and does not develop solely as a result of glaucoma damage.

Predicting the Onset of Glaucoma: The Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study

OBJECTIVE To evaluate the predictive ability of baseline confocal scanning laser ophthalmoscopy (CSLO) Glaucoma Probability Score (GPS) for the development of primary open-angle glaucoma (POAG) and to compare it with the Moorfields regression analysis (MRA) classification, other topographic optic disc parameters, and stereophotograph-based cup-to-disc ratio. DESIGN Longitudinal, randomized clinical trial. PARTICIPANTS We included 857 eyes of 438 participants in the CSLO Ancillary Study to the Ocular Hypertension Treatment Study (OHTS) with good quality baseline CSLO images. METHODS The ability of baseline GPS, MRA, and optic disc parameters to predict the development of POAG was evaluated in univariate and multivariable proportional hazard ratio analyses. Likelihood ratios and positive and negative predictive values were compared. MAIN OUTCOME MEASURES The POAG end point as determined by repeatable changes in the visual field or optic disc. RESULTS Sixty-four eyes of 50 CSLO Ancillary Study participants developed POAG. Median time to reach a POAG end point was 72.3 months. The 93 eyes of 388 participants not reaching endpoint were followed for a median of 124.9 months. Baseline GPS identified many more eyes as outside normal limits than the MRA. In multivariable analyses, all regional and global baseline GPS indices were significantly associated with the development of POAG; hazard ratios (95% confidence interval) ranged from 2.92 to 3.74 for an outside normal limits result. The MRA indices were also significantly associated with the development of POAG in multivariable analyses. In addition, the predictive ability of baseline GPS, MRA and stereometric parameters were similar to the predictive ability of models using photograph-based horizontal cup-to-disc ratio. CONCLUSIONS These results suggest that baseline GPS, MRA, and stereoparameters alone or when combined with baseline clinical and demographic factors can be used to predict the development of POAG end points in OHTS participants and are as effective as stereophotographs for estimating the risk of developing POAG in ocular hypertensive subjects.

Comparison of Phacotrabeculectomy With 5-Fluorouracil, Mitomycin-C, and Without Antifibrotic Agents

BACKGROUND AND OBJECTIVE To evaluate the potential benefits, complications, and prognostic risk factors for failure of phacotrabeculectomy performed with or without 5-fluorouracil (5-FU) and mitomycin-C (MMC). PATIENTS AND METHODS Retrospective chart review of 78 patients who underwent phacotrabeculectomy during a 2-year period. Patients were divided into 3 groups, those who received 5-FU (N = 28). MMC (N = 29), or no antifibrotic agent (N = 21). RESULTS All 3 groups had statistically significant lower intraocular pressures (IOP) on fewer antiglaucomatous medications at 6-month, 12-month, and last follow-up compared to preoperative levels (P < .05). Intraocular pressures were lower in the group that received MMC compared to the 5-FU group, but not in the group that did not receive antimetabolites, at all time intervals measured (P < .05). Black race was a strong predictor of failure of trabeculectomy (P = 009). No differences in final visual acuity or complications were found between groups. CONCLUSIONS Phacotrabeculectomy is effective regardless of antimetabolite use. Race is a strong predictor of failure.

Association between lower optic nerve laser Doppler blood volume measurements and glaucomatous visual field progression

Aim: To perform a preliminary assessment of the relation between optic nerve circulatory parameters and glaucomatous visual field progression. Methods: This study included 29 eyes of 23 patients with open angle glaucoma that had typical glaucomatous nerve fibre bundle visual field defects and increased cup to disc ratios. Laser Doppler flowmetry (Oculix) was used to measure relative optic nerve blood volume (Vol), velocity (Vel) and flow in the superior temporal (ST) and inferior temporal (IT) neuroretinal rim of the optic nerve. After blood flow measurements patients were followed for 6–62 months (mean 33 (SD 17) months) and 2–11 Humphrey visual fields (4.7 (2.6) fields) were obtained. Progression of glaucoma was assessed by the slope of the corrected pattern standard deviation (CPSD) values versus time, which was calculated manually for each eye using regression analysis. Results: A significant negative correlation was observed between Vol in the IT rim and the CPSD slope (r = −0.56, p = 0.002); patients with lower Vol tended to show faster progression of glaucomatous field damage than those with higher Vol. When the eyes were arbitrarily divided into two groups according to lower Vol (0.32 (0.06) arbitrary units, AU, n = 15) or higher Vol (0.49 (0.06) AU, n = 14), those with lower Vol had significantly worse mean CPSD slopes (0.50 (0.48) dB/year) than those with higher Vol (−0.67 (1.38) dB/year; Student’s t test, p = 0.009). Conclusions: In the IT rim, the area most prone to develop glaucomatous field damage, lower Vol is associated with subsequently faster CPSD progression. These measurements suggest that circulatory abnormalities may have a role in the development of glaucoma.

Association of Retinal Vessel Caliber and Visual Field Defects in Glaucoma

PURPOSE This study evaluates the asymmetry of peripapillary retinal vessel caliber between inferior and superior hemispheres in eyes with visual field defects predominantly in one hemifield. DESIGN Observational case series. METHODS In a retrospective study, 64 eyes of 64 patients with primary open-angle glaucoma who had a marked difference in visual field defects between hemifields and who had no history of diabetes, trauma, or vascular occlusive disease were studied. The diameters of the superior and inferotemporal vessels were measured at the optic disk border with calipers on an enlarged image. RESULTS In 64 eyes, the average ratio of the superior temporal artery diameter to inferotemporal artery diameter was significantly greater in the eyes with predominantly superior visual field defects as compared with those with inferior defects (1.10 +/- 0.22 vs. 0.92 +/- 0.19, respectively, P =.002, two-tailed t test). This indicates that the arteriole corresponding to the hemifield with the greater visual field defect was narrower than the arteriole in the other hemifield. This relationship was confirmed using chi(2) analysis (P =.002) comparing the proportions of eyes with ratios greater or less than normal vessel caliber ratios (normal ratio = 0.95 from data reported by Jonas and associates to the location of the dominant field defect. No statistically significant relationship was detected between retinal vein diameter and localized visual field defects, as determined by both the unpaired t test and chi(2) analysis. CONCLUSION In eyes with primary open-angle glaucoma, this study demonstrates a strong association between decreased peripapillary arteriole diameter and visual field defects in the corresponding hemifield. This reflects either an ischemic basis for glaucomatous damage or vascular constriction when there are fewer axons to nourish.

Laser Doppler Flowmetry of the Optic Nerve Head in Glaucoma

The introduction of ocular laser Doppler flowmetry during the last decade has greatly improved our ability to noninvasively assess the hemodynamics of the optic nerve in patients with glaucoma. Studies with laser Doppler flowmetry have determined that blood flow in the optic nerve is diminished in eyes with primary open-angle glaucoma and that this decrease occurs in patterns consistent with glaucomatous damage. Lower systemic blood pressure is associated with lower blood flow, supporting numerous studies linking systemic hypotension to glaucomatous damage. This direct relationship between systemic blood pressure and optic nerve blood flow has significant implications in terms of the etiology of glaucomatous damage and the treatment of ocular and systemic diseases in the glaucoma patient. Further research is needed to determine whether the circulatory abnormalities of the optic nerve head are a cause or a result of glaucomatous damage.

Effect of Intravenous Fenoldopam on Intraocular Pressure in Ocular Hypertension

Intravenous fenoldopam, a selective dopamine‐1 receptor agonist, was compared with placebo in this randomized, double‐blind, two‐period crossover study to evaluate its effects on intraocular pressure, aqueous dynamics, and macular blood flow in patients with elevated intraocular pressure or primary open‐angle glaucoma. Doses of fenoldopam were titrated up to a maximum of 0.5 μg/kg/min. Intraocular pressure, measured by pneumotonometry, was the primary outcome variable. Other outcomes included macular blood flow assessed by blue field examination, visual field examined by automated perimetry, aqueous outflow facility measured by tonography, and aqueous humor production determined by fluorophotometry. During infusions of fenoldopam, intraocular pressure increased from a mean baseline level of 29.2 mmHg to a mean maximum level of 35.7 mmHg. During the placebo infusions, pressure increased from a mean baseline of 28.4 mmHg to a mean of 29.0 mmHg at the time point that corresponded to the mean maximum intraocular pressure on the day intravenous fenoldopam was administered, to yield a mean difference in pressure between study days of 6.7 mmHg (P <0.05). There were no apparent changes in macular blood flow, visual fields, or production or outflow of aqueous humor associated with fenoldopam infusion. The increase in intraocular pressure seen in this population of patients with ocular hypertension during infusions of fenoldopam is consistent with fenoldopam‐associated increases in intraocular pressure reported in previous studies of healthy volunteers and of patients with accelerated systemic hypertension. These results further suggest that dopamine‐1 receptors play a role in the regulation of intraocular pressure.

Laser Doppler Flowmetry in Asymmetric Glaucoma

Purpose. To evaluate the relationship between extent of glaucoma damage and optic nerve blood flow, we investigated optic nerve head blood flow in patients with asymmetric glaucoma damage between their two eyes and also in glaucomatous eyes with asymmetric damage inferiorly versus superiorly. Methods. From our institutional practice, 16 subjects with asymmetric glaucoma damage between their two eyes and 25 eyes of 20 patients with asymmetric damage superiorly versus inferiorly were included in the study. Determinations of relative optic nerve head blood flow, velocity, and volume were obtained with laser Doppler flowmetry in the superotemporal and inferotemporal neuroretinal rim and in the cup. Means of flow (Flow3), velocity (Vel3), and volume (Vol3) were calculated from these three measurement sites, and eyes or hemidisks with greater glaucomatous damage were compared to eyes or hemidisks with less damage. Results. For subjects with asymmetric glaucoma damage between eyes, Flow3 and Vel3 were significantly lower in the eyes with worse glaucoma damage (mean difference=2.09, p=0.005, and mean difference=0.05, p=0.002, respectively). When comparing optic disks displaying within-eye asymmetry, the hemidisk with greater damage showed significantly lower blood velocity than the hemidisk with less damage (mean difference=0.05, p=0.013); however, no difference in blood flow or volume was detected. Conclusions. This study provides additional evidence that impaired optic nerve circulation is associated with the extent of glaucomatous pathology.

An unusual case of uveitis-glaucoma-hyphema syndrome

PURPOSE To report a case of uveitis-glaucoma-hyphema (UGH) syndrome in which anterior chamber paracentesis led to the diagnosis of sickle cell trait. DESIGN Observational case report. METHODS A 43-year-old Cuban pseudophakic male was seen multiple times over a 3-year period complaining of floaters and blurry vision in his left eye. He was noted to have an inferotemporally displaced posterior chamber intraocular lens and recurrent microhyphemas with elevated intraocular pressure (IOP) readings between 29 and 46 mm Hg with each episode. He was diagnosed with UGH syndrome. Posterior chamber intraocular lens explantation and anterior chamber washout was performed. The aqueous fluid was submitted for cytopathologic examination. RESULTS Postoperatively, the patients symptoms resolved and he had no further hemorrhages or elevated IOP readings. Cytopathology of the aspirate revealed sickled red blood cells. CONCLUSIONS Microscopic examination of aqueous fluid can be a valuable tool in diagnosing ophthalmic manifestations of systemic disease.

Utility of Digital Stereo Images for Optic Disc Evaluation

PURPOSE To assess the suitability of digital stereo images for optic disc evaluations in glaucoma. METHODS Stereo color optic disc images in both digital and 35-mm slide film formats were acquired contemporaneously from 29 subjects with various cup-to-disc ratios (range, 0.26-0.76; median, 0.475). Using a grading scale designed to assess image quality, the ease of visualizing optic disc features important for glaucoma diagnosis, and the comparative diameters of the optic disc cup, experienced observers separately compared the primary digital stereo images to each subjects 35-mm slides, to scanned images of the same 35-mm slides, and to grayscale conversions of the digital images. Statistical analysis accounted for multiple gradings and comparisons and also assessed image formats under monoscopic viewing. RESULTS Overall, the quality of primary digital color images was judged superior to that of 35-mm slides (P < 0.001), including improved stereo (P < 0.001), but the primary digital color images were mostly equivalent to the scanned digitized images of the same slides. Color seemingly added little to grayscale optic disc images, except that peripapillary atrophy was best seen in color (P < 0.0001); both the nerve fiber layer (P < 0.0001) and the paths of blood vessels on the optic disc (P < 0.0001) were best seen in grayscale. The preference for digital over film images was maintained under monoscopic viewing conditions. CONCLUSIONS Digital stereo optic disc images are useful for evaluating the optic disc in glaucoma and allow the application of advanced image processing applications. Grayscale images, by providing luminance distinct from color, may be informative for assessing certain features.