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To identify precursors of macular atrophy (MA) and of fibrotic scar (FS) in eyes treated with anti-vascular endothelial growth factor through pixel-mapping analysis of baseline optical coherence tomography (OCT).Design: Cross-sectional analysis.Multicenter clinical trial.68 eyes from the Comparison of Age-Related Macular Degeneration Treatments Trials.Treatment with anti-vascular endothelial growth factor agents.The percentage of MA or FS pixels with each OCT feature at baseline, and the odds ratio for baseline pixels with an OCT feature to develop MA or FS.Retinal pigment epithelium atrophy and photoreceptor loss on OCT were highly predictive of MA at that location at years 2 and 5 (P.0001), but accounted for only 22.5% of the ensuing atrophy at year 2 and less at year 5. Among pixels of MA at year 2, 78% were preceded by thick drusen, 54% by subretinal macular neovascularization (MNV), and 22.5% by no detectable OCT features. MNV, subretinal hyperreflective material, pigment epithelial detachment, intraretinal fluid, and sub-retinal pigment epithelium fluid were predictive of FS at that location (P values.05). More than 75% of the pixels of FS at years 2 and 5 were preceded by pixels of baseline MNV.Most pixels of FS were preceded by components of neovascularization. Although one-quarter of MA was accounted for by pre-existing evidence of atrophy on OCT alone, the development of MA in areas of thick drusen, areas with and without subretinal MNV lesion, and areas without detectable OCT precursors argues that the development of MA is multifactorial and may follow, in part, a non-neovascular pathway.

PURPOSE: Sildenafil citrate induces vasodilation by enhancing the smooth muscle relaxant effects of nitric oxide. We have previously reported that nitrate compounds, a different group of nitric oxide–mediated vasodilators used mainly for the treatment of ischemic cardiac diseases, produce an increase in optic nerve head circulation and retinal venous vasodilation. The purpose of the present investigation was to evaluate the effect of sildenafil on ocular circulation. METHODS: In a double-blind, randomized, crossover trial, 15 healthy male volunteers received 100-mg doses of sildenafil citrate (Viagra; Pfizer, Inc, New York, New York) or matching placebo on 2 separate days. Laser Doppler flowmetry was used to assess foveolar choroidal and optic nerve rim circulatory parameters. Measurements were obtained in one eye at baseline, 1 hour, and 5 hours after dosing. Blood pressure and intraocular pressure were monitored, and perfusion pressure was calculated. RESULTS: Mean optic nerve head blood flow measurements at baseline, 1 hour, and 5 hours were 11.6 ± 2.2 arbitrary units (± SD), 12.5 ± 2.8, and 12.1 ± 2.4 after sildenafil and 11.9 ± 2.5, 12.6 ± 3.1, and 13.0 ± 3.0 after placebo, respectively. When compared with placebo, no significant change in mean blood pressure, intraocular pressure, perfusion pressure, or choroidal or optic nerve circulatory parameters were observed after sildenafil treatment. The power to detect a 20% change in optic nerve head and choroidal blood flow after sildenafil was approximately 90%. CONCLUSIONS: In comparison with placebo, no significant change in optic nerve rim or foveolar choroidal blood flow was observed after treatment with sildenafil. This suggests that nitrate compounds and sildenafil may differentially affect ocular circulation. Furthermore, no significant effects on intraocular pressure, systemic blood pressure, or ocular perfusion pressure were detected after sildenafil treatment.

PURPOSE: To investigate retinal circulatory changes that occur during the third trimester of pregnancy in diabetic patients and control subjects. METHODS: Bidirectional laser Doppler velocimetry and monochromatic fundus photography were used to assess the retinal circulation in seven pregnant diabetic patients and 13 age-matched pregnant control subjects. Retinal venous diameter (D), maximum erythrocyte velocity (Vmax), and retinal volumetric blood flow rate (Q) were measured in one eye of each subject during the third trimester of pregnancy (DPREG, VmaxPREG, and QPREG, respectively). These measurements were repeated during the postpartum period for both diabetic patients (11 ± 7 weeks postpartum) and control subjects (16 ± 6 weeks postpartum; P = .203; DPOST, VmaxPOST, and QPOST). RESULTS: In control subjects, DPREG was significantly reduced by −4.5% ± 4.4% (mean percent difference ± 1 standard deviation; paired t test, P = .006) relative to DPOST. In diabetic women, DPREG was also significantly reduced by −8.1% ± 3.2% compared with DPOST ( P = .001), a change that was significantly larger than that seen in control subjects (unpaired t test; P = .035). Compared with QPOST, QPREG was reduced by −7.1% ± 14.2% ( P = .123), in control subjects. In diabetic women, QPREG was significantly decreased by −18.4% ± 9.3% compared with QPOST ( P = .012). This reduction in QPREG was significantly greater in diabetic patients than in nondiabetic control subjects (unpaired t test, P = .040). No significant differences between VmaxPREG and VmaxPOST were observed in either diabetic patients (−3.1% ± 12.9%; P = .400) or control subjects (+1.9% ± 14.4%; P = .787). CONCLUSIONS: Retinal venous diameter is decreased during the third trimester of pregnancy in both diabetic and nondiabetic mothers. This decrease is significantly larger in diabetic than in nondiabetic mothers. In addition, we observed a reduction in retinal volumetric blood flow in diabetic patients during pregnancy that was significantly larger than that present in nondiabetic women. This fall in retinal volumetric blood flow in diabetic patients may exacerbate retinal ischemia and hypoxia and thus may be associated with the progression of diabetic retinopathy.

To investigate optic nerve head blood flow in patients with glaucoma and to assess the effect of systemic hypertension.This study included 24 eyes of 24 patients with primary open-angle glaucoma. Eleven of these patients had a history of systemic hypertension. Results in patients with glaucoma were compared with those of 13 eyes of 13 age-matched normal controls. Determinations of relative optic nerve head blood velocity, volume, and flow were obtained with laser Doppler flowmetry in the superotemporal and inferotemporal neuroretinal rim and also in the cup. Means of the velocity, volume, and flow of these three measurement sites were calculated for each subject.Mean overall optic nerve head blood flow was 29% lower in glaucoma patients than in normal controls (t test, P.001). This decrease in flow was mainly caused by a decrease of 23% in mean blood velocity (P.001). Mean flow in glaucoma patients without systemic hypertension was 26% lower than that of glaucoma patients with hypertension (Tukey honest significant difference test, P = .05). A significant direct correlation was observed between mean flow and mean blood pressure (R = 0.51, P.02).Optic nerve blood flow is reduced in glaucoma patients. Glaucoma patients without systemic hypertension have lower optic nerve blood flow than those with hypertension. Our results raise concerns that treatment of systemic hypertension may further decrease optic nerve blood flow in glaucoma patients.

Purpose To evaluate the feasibility of using semiautomated analysis of digital fundus images to quantify effects of photocoagulation on retinal vessel diameter in retinopathy of prematurity (ROP). Design Case series. Methods Fourteen eyes of seven patients with threshold ROP and 12 eyes of six controls were included. Fundus images were captured before and after photocoagulation, or one to three weeks apart in controls, using an NM200D camera (Nidek, Inc, Aichi, Japan). VesselMap software (Imedos, Jena, Germany) measured vessel diameter. The t test analysis was used to assess vessel changes. Results The authors observed a significant reduction in average largest retinal vein diameter of −18% ± 16% (±1 standard deviation). The average largest artery diameter trended down by −12% ± 16%. Compared with controls, diameter reduction was significant in veins ( P = .014) and arteries ( P = .016). Conclusions The diameter of retinal vessels decreases after photocoagulation. VesselMap analysis of digital images is feasible and may be helpful in quantifying treatment effects.

Purpose A recent report has suggested that nitrate therapy may delay the progression of glaucomatous damage. To investigate the mechanism that may mediate this effect, we sought to determine whether nitrate therapy is associated with retinal vasodilatation in patients with glaucoma. Methods Retinal venous and arterial diameters were determined from color fundus photographs of the optic nerve head obtained during a retrospective study designed to investigate any potential effects of chronic nitrate treatment on the progression of glaucomatous pathology. Fourteen eyes of 14 patients who were receiving chronic nitrate therapy for systemic diseases unrelated to glaucoma were randomly selected. Vascular measurements were compared with those of 15 eyes of 15 control patients with glaucoma who did not receive any nitrate therapy. Results In comparison with control patients, nitrate-treated patients showed significant average vasodilatation of 17% ( P = .008) and 13% ( P = .01) in the superior and inferior temporal retinal veins, respectively. A 5% increase in average retinal arterial diameter was also detected, but this was not statistically significant. Conclusion Chronic nitrate treatment is associated with retinal venous dilatation in patients with glaucoma. Although not assessed in this study, it is possible that a protective effect of nitrates may be mediated by a vasoactive effect leading to improved perfusion of the retina and perhaps the optic nerve head, in a similar fashion to what has been observed in the circulation of the heart. Additional studies of the effect of nitrates on the ocular circulation are needed, however, to support this speculation.

To investigate the relationship between known risk factors for age-related macular degeneration (AMD) progression and foveolar choroidal circulation in eyes with nonexudative AMD.Cross-sectional study of nonexudative AMD.Laser Doppler flowmetry measurements of relative choroidal blood velocity, choroidal blood volume (ChBVol), and choroidal blood flow (ChBFlow) were obtained in the center of the fovea of 273 study eyes of 204 AMD patients investigated at the Scheie Eye Institute, University of Pennsylvania Medical School. All study eyes had visual acuity of 20/40 or better, good fixation, no other intraocular pathologic features, and no evidence of choroidal neovascularization. RPE hypertrophy was determined from color fundus photographs by trained masked graders at the Scheie Image Reading Center. Correlation analysis and multivariate linear regression analysis with adjustments for significant covariates were carried out.A significant inverse correlation was observed between age and ChBFlow (r = -0.36; P.0001), and ChBVol (r = -0.28; P.0001), but not for choroidal blood velocity. A significant inverse correlation was observed between spherical equivalent and ChBFlow (r = -0.21; P = .006) and ChBVol (r = -0.14; P = .04), but not for choroidal blood velocity. ChBFlow and ChBVol were significantly lower in patients with a history of hypertension (Por = .003) and in eyes with retinal pigment epithelium hypertrophy (Por = .04), respectively.All the above-described risk factors for AMD development and progression are associated with decreased choroidal circulatory parameters, suggesting that decreases in choroidal circulatory parameters may be involved in the development of AMD.

Purpose To determine the feasibility of using semiautomated analysis of digital fundus images to quantify the differences in retinal vascular diameter between retinopathy of prematurity (ROP) patients with and without plus disease. Design Case-control study. Methods Thirty eyes of 15 patients with ROP were included in this study. Fourteen eyes of seven patients had plus disease and 16 eyes of eight patients had no evidence of plus disease. Digital fundus images were captured using an NM200D (Nidek, Inc, Aichi, Japan) camera. Vessel diameters were determined using VesselMap software (Imedos, Jena, Germany). The Student t test analysis was used to compare diameters of vessels with and without plus disease. Results We found that the average venous diameter is significantly larger by 15% in the group with plus disease. Conclusions VesselMap analysis of digital images is feasible. This method is able to distinguish between veins with and without plus disease, and may be useful in telemedicine screening strategies.

Purpose To determine whether laser treatment applied according to the complications of age-related macular degeneration prevention trial (CAPT) has an effect on the choroidal circulation. Design Randomized controlled trial. Methods This study included 30 CAPT patients with bilateral drusen. Laser Doppler flowmetry was used to measure relative choroidal blood flow (Ch flow ) in the fovea. Measurements were obtained through dilated pupils in both eyes of each patient before photocoagulation was applied in one eye. Measurements were repeated at three months (30 patients) and 28 months (23 patients). Results Average Ch flow at baseline, three months, and 28 months was 7.2 ± 2.1 (±1 SD), 7.3 ± 2.5, and 6.8 ± 2.7 arbitrary units (AU) in the control eyes and 6.6 ± 1.6, 7.0 ± 2.3, and 7.8 ± 3.0 AU in the treated eyes. In comparison to control eyes, there was no significant change in Ch flow in the treated eyes at three months after treatment. At 28 months, however, there was a 5.6% drop in Ch flow in control eyes and an 18.2% increase in Ch flow in treated eyes from baseline. The average difference of 23.8% between the percentage changes in Ch flow observed in the control and treated eyes was statistically significant (paired two-tailed Student t test; P = .05). Conclusions Our results suggest an increase in choroidal blood flow 28 months after laser treatment according to the CAPT protocol. This increase may play a role in the mechanism leading to the disappearance of drusen after photocoagulation. Whether removal of drusen after photocoagulation is beneficial to the patients is not known at this time.

PURPOSE: The present investigation was conducted to evaluate the effect of sildenafil citrate (Viagra, Pfizer Inc., New York, NY) on retinal blood vessel diameter. DESIGN: Double-blind randomized, placebo-controlled, cross-over study. METHODS: Fifteen healthy male volunteers (mean age 39 years) received 100-mg doses of sildenafil or matching placebo on 2 separate days. Monochromatic fundus photography was obtained in one eye, and brachial artery blood pressure and intraocular pressure were measured at baseline, 1 hour, and 5 hours after dosing. The diameters of two major temporal veins and one artery were measured in a masked fashion from digitized photographic negatives. RESULTS: In comparison with placebo, no statistically significant change in average venous diameter was observed for the superior (analysis of variance [ANOVA], P = .97), inferior retinal temporal vein (ANOVA, P = .73), or the retinal temporal artery (ANOVA, P = .89) after sildenafil treatment. In comparison to placebo, there was no significant difference in the percentage change from baseline in venous or arterial diameter at 1 or 5 hours after sildenafil. The power to detect a 6.5% change in retinal vascular diameter following sildenafil was approximately 80% ( P = .05). CONCLUSIONS: These data suggest that at the maximum therapeutic dose used clinically (100 mg), sildenafil does not have a significant effect on retinal vascular caliber.

PURPOSE: To assess the acute effects of sildenafil citrate (VIAGRA) on the intraocular pressure (IOP) of patients with chronic open-angle glaucoma. DESIGN: This was a double-blind, randomized, placebo-controlled, crossover study, in which 15 patients received a single oral dose of sildenafil 100 mg or matching placebo on two separate occasions. METHODS: Fifteen subjects aged 63 ± 14 years (mean ± SD) with bilateral chronic open-angle glaucoma were administered a single oral dose of sildenafil 100 mg or matching placebo on two separate occasions at least 3 days apart. IOP was measured in both eyes by Goldmann ap-planation tonometry at baseline and then at 1–5 hours after dosing. Brachial artery systolic and diastolic blood pressures were determined by sphygmomanometry, and heart rate was also monitored at baseline and 1–5 hours after dosing. RESULTS: Compared with placebo, no statistically or clinically significant change in IOP was detected after a single dose of sildenafil 100 mg ( P = .20). Moreover, no significant change in mean systemic blood pressure ( P = .12) or heart rate ( P = .72) was detected after treatment with sildenafil. CONCLUSION: At the maximum therapeutic dose of 100 mg, sildenafil did not produce any significant acute change in IOP in men with chronic open-angle glaucoma. This information is of importance for patients with glaucoma receiving sildenafil for treatment of erectile dysfunction.

PURPOSE: To assess the short-term effects of sildenafil citrate on intraocular pressure in healthy male volunteers and participants in clinical trials. METHODS: Intraocular pressure and pupil diameter were measured in two placebo-controlled studies. Oral doses of sildenafil citrate (VIAGRA; Pfizer Inc, New York, New York) ranged from 10 mg to 150 mg. RESULTS: No major changes in intraocular pressure or pupillometry were detected at any time (1.0–24 hours) after administration of sildenafil. Additionally, of 36 subjects with a medical history of increased intraocular pressure in the sildenafil safety database, none were reported to have a clinically significant increase of their intraocular pressure. During clinical trials, two glaucoma cases were listed as serious adverse events, but were not considered treatment related. CONCLUSION: No clinical abnormalities were observed in intraocular pressure or pupil diameter in subjects receiving sildenafil. Currently, no evidence suggests that long-term treatment with sildenafil has an effect on intraocular pressure or is associated with the development or worsening of glaucoma.

PURPOSE: To describe the clinical features and complications of diabetic retinopathy, visual acuity, and number of repeat treatments after panretinal photocoagulation for proliferative diabetic retinopathy in a tertiary care center. METHODS: A cohort study was conducted with data collection from medical records of patients undergoing panretinal photocoagulation between 1985 and 1995 at the Scheie Eye Institute; 297 eyes of 186 patients were eligible for study. RESULTS: The presence of neovascularization of the disk at baseline, an earlier onset of diabetes, and a shorter duration of disease before panretinal photocoagulation were the strongest risk factors for needing an additional panretinal photocoagulation treatment. Sixty-two percent of eyes with poor visual acuity (≤20/200) at baseline still had poor visual acuity at 1 year, and 76% with good visual acuity (≥20/40) at baseline maintained good visual acuity at 1 year. Poor vision at baseline was the only risk factor for having poor vision at 1 year. Vitreous hemorrhage was present in 44% of eyes at baseline. New vitreous hemorrhage developed in 37% of eyes during the first year after panretinal photocoagulation. A traction retinal detachment was present in 4% of eyes at baseline and newly developed in 6% of eyes during follow-up. A repeat panretinal photocoagulation treatment was performed in 39% of eyes after initial treatment. A vitrectomy was performed in 10% of eyes from baseline through the 1-year follow-up visit. CONCLUSIONS: The data from this study are useful for counseling patients with respect to likely visual outcome, possibility of major complications from proliferative diabetic retinopathy, and the chance of undergoing additional laser treatment after panretinal photocoagulation.

Purpose To assess whether the rate of change of retinal vessel diameter can help identify infants at the highest risk for severe retinopathy of prematurity (ROP). Design Thirty-five infants at risk for ROP were included in this prospective, longitudinal study. Methods Images were obtained using the NIDEK NM200D noncontact camera (NIDEK Inc, Aichi, Japan) at the time of ROP examinations in the intensive care unit. Vessel diameters were measured from digital fundus photographs of right eyes in a masked fashion using VesselMap image analysis software (IM-EDOS GmbH, Weimar, Germany). The rate of change of vessel diameter was calculated based on the linear regression slope and was compared between eyes in which type 1 ROP requiring treatment developed and in controls without ROP or with ROP less severe than type 1. Results Multivariate analysis showed that the group of eyes in which type 1 ROP developed had a greater increase in diameter over time in the inferior temporal veins ( P = .01), superior temporal veins ( P P P = .02), and mean temporal arteries ( P = .004). The area under receiver operator characteristic curve for venous diameter change was 0.96 for the superior temporal vein, 0.86 for the inferior temporal vein, and 0.96 for the mean temporal vein. Conclusions On average, the rate of retinal vessel change was greater in eyes with type 1 ROP requiring treatment than in control eyes. The rate of venous diameter change had the best discriminative ability to differentiate between the 2 groups.