Luciano Quaranta

Effect of Ginkgo biloba extract on preexisting visual field damage in normal tension glaucoma

OBJECTIVE To evaluate the effect of Ginkgo biloba extract (GBE) on preexisting visual field damage in patients with normal tension glaucoma (NTG). DESIGN Prospective, randomized, placebo-controlled, double-masked cross-over trial. PARTICIPANTS Twenty-seven patients with bilateral visual field damage resulting from NTG. INTERVENTION Patients received 40 mg GBE, administered orally, three times daily for 4 weeks, followed by a wash-out period of 8 weeks, then 4 weeks of placebo treatment (identical capsules filled with 40 mg fructose). Other patients underwent the same regimen, but took the placebo first and the GBE last. Visual field tests, performed at baseline and at the end of each phase of the study, were evaluated for changes. MAIN OUTCOME MEASURES Change in visual field and any ocular or systemic complications. RESULTS After GBE treatment, a significant improvement in visual fields indices was recorded: mean deviation (MD) at baseline versus MD after GBE treatment, 11.40 +/- 3.27 dB versus 8.78 +/- 2.56 dB (t = 8.86, P = 0.0001, chi-square test); corrected pattern standard deviation (CPSD) at baseline versus CPSD after GBE treatment, 10.93 +/- 2.12 dB versus 8.13 +/- 2.12 dB (t = 9.89, P = 0.0001, chi-square test). No significant changes were found in intraocular pressure, blood pressure, or heart rate after placebo or GBE treatment. Any ocular and systemic side effects were recorded for the duration of the trial. CONCLUSIONS Ginkgo biloba extract administration appears to improve preexisting visual field damage in some patients with NTG.

24-hour Intraocular Pressure and Ocular Perfusion Pressure in Glaucoma

This review analyzes the currently available literature on circadian rhythms of intraocular pressure (IOP), blood pressure, and calculated ocular perfusion pressure (OPP) in patients with open-angle glaucoma. Although adequately powered, prospective trials are not available. The existing evidence suggests that high 24-hour IOP and OPP fluctuations can have detrimental effects in eyes with glaucoma. The currently emerging continuous IOP monitoring technologies may soon offer important contributions to the study of IOP rhythms. Once telemetric technologies become validated and widely available for clinical use, they may provide an important tool towards a better understanding of long- and short-term IOP fluctuations during a patients daily routine. Important issues that need to be investigated further include the identification of appropriate surrogate measures of IOP and OPP fluctuation for patients unable to undergo 24-hour measurements, the determination of formulae that best describe the relationship between systemic blood pressure and IOP with OPP, and the exact clinical relevance of IOP and OPP fluctuation in individual patients. Despite the unanswered questions, a significant body of literature suggests that OPP assessment may be clinically relevant in a significant number of glaucoma patients.

Color Doppler imaging of ophthalmic artery blood flow velocity: A study of repeatability and agreement

PURPOSE Color Doppler imaging (CDI) is a relatively new technique that allows quantification of blood flow velocity in orbital and ocular vasculature. Despite the numerous clinical studies that have used CDI, repeatability of this technique and agreement between observers have not been documented. METHODS The authors performed a prospective investigation of the repeatability and agreement between observers on ophthalmic artery blood flow velocity measurements in 35 patients (35 eyes). RESULTS Results on the estimated error of measurement (variability between repeated readings on the same subject) indicate good repeatability of the measurements; in fact, the measurement variances were only 5.6% for the peak systolic velocity, 11.4% for the end diastolic velocity, and 6.2% for the mean envelope velocity. The statistical analysis of repeatability showed a very narrow 95% confidence interval for both observers. The measurement of agreement between the two observers demonstrated the existence of a good concordance of the measurements taken by each observer on each subject. CONCLUSIONS Results suggest that CDI is a reliable tool for quantitative assessment of ophthalmic artery blood flow velocity.

Efficacy and Safety of Trabeculectomy vs Nonpenetrating Surgical Procedures: A Systematic Review and Meta-analysis

IMPORTANCE To date, only a few studies have directly compared nonpenetrating surgery (NPS) and trabeculectomy (TE). Therefore, there is no strong evidence as to which surgical technique leads to the best results in terms of ocular hypotensive effect and safety. OBJECTIVE To compare the hypotensive effect and safety of NPS and TE in terms of intraocular pressure (IOP) reduction and incidence of complications. DATA SOURCES The MEDLINE and EMBASE databases were searched for studies potentially eligible in any language published up to March 31, 2013. STUDY SELECTION Systematic review and meta-analysis of comparative studies of 2 or more surgical techniques (1 of which had to be TE), including patients with open-angle glaucoma. DATA EXTRACTION AND SYNTHESIS The considered interventions were TE, deep sclerectomy (DS), viscocanalostomy, and canaloplasty. MAIN OUTCOMES AND MEASURES The primary outcome was the mean between-group difference in the reduction in diurnal IOP from baseline to the 6- or 12-month follow-up evaluation. We also considered the incidence of complications, expressed as relative risk. RESULTS Eighteen articles, accounting for 20 comparisons, were selected for data extraction and analysis. Analysis of the 6-month follow-up data showed that the pooled estimate of the mean between-group difference was -2.15 mm Hg (95% CI, -2.85 to -1.44) in favor of TE. There was no difference between the NPS subgroups. In the subgroup antimetabolite analysis, the addition of mitomycin C to TE and DS decreased the difference in the reduction in IOP (TE and DS without mitomycin C: -2.65 mm Hg [95% CI, -3.90 to -1.39]; TE and DS with mitomycin C: -0.83 mm Hg [95% CI, -2.40 to 0.74]). In the subgroup analysis by implant addition, no significant difference induced by DS with or without drainage devices was detected (test for subgroup differences: χ(2)(1) = 0.24; P = .62). The absolute risk of hypotony, choroidal effusion, cataract, and flat or shallow anterior chamber was higher in the TE group than in the NPS group. CONCLUSIONS AND RELEVANCE Trabeculectomy seems to be the most effective surgical procedure for reducing IOP in patients with open-angle glaucoma. However, as expected, it was associated with a higher incidence of complications when compared with NPS.

Prostaglandin analogs and timolol-fixed versus unfixed combinations or monotherapy for open-angle glaucoma: A systematic review and meta-analysis

PURPOSE To estimate the intraocular pressure (IOP)-lowering effect of prostaglandin analogs (PGAs) administered in combination with β-blockers. METHODS We searched the Medline and Embase databases for randomized trials comparing topical therapies with PGAs and timolol administered as monotherapy (Mt), or in fixed (FC) or unfixed combinations (UC) to patients with glaucoma or ocular hypertension. The efficacy endpoint was the mean difference (MeD) in the reduction in IOP from baseline; the tolerability endpoint was the incidence of hyperemia. RESULTS The 18 eligible trials involved 23 comparisons of FC versus Mt, and 5 of FC versus UC. The FCs were less efficacious than UCs (MeD: 0.69, 95% CI: 0.29 to 1.08). In comparison with timolol Mt, the latanoprost/timolol FC led to a greater IOP reduction (MeD: -2.74, 95% CI: -3.24 to -2.23) than the bimatoprost/timolol FC (MeD: -1.49, 95% CI: -1.86 to -1.12) or the travoprost/timolol FC (MeD: -1.93, 95%CI: -2.98 to -0.88). The FCs led to a lower hyperemia risk than UCs [relative risk (RR): 0.70, 95% CI: 0.43 to 1.14] and PGA Mt (RR: 0.61, 95% CI: 0.53 to 0.70). CONCLUSIONS FCs are more efficacious than their individual components, but less efficacious than their respective UCs. FCs lead to a lower hyperemia risk than UCs and their respective PGA Mts.

Peak Intraocular Pressure and Glaucomatous Progression in Primary Open-Angle Glaucoma

PURPOSE To evaluate the effect of 24-h peak intraocular pressure (IOP) on the progression of primary open-angle glaucoma (POAG) and the 24 h time points that best predict peak pressure. METHODS A retrospective analysis of clinical data evaluating long-term glaucomatous progression in patients with POAG who were previously in a 24-h study of the authors (IOP readings at 2/6/10 A.M. and 2/6/10 PM); had ≥3 treated 10 A.M. (±1 h) IOP measurements over 5-years after an untreated 24-h baseline; and had a treated 24-h curve with a 10 A.M. IOP±2 mmHg within the 10 A.M. mean IOP over 5-years. RESULTS We included 98 nonprogressed and 53 progressed patients with POAG (n=151). The mean 24-h peak IOP (mmHg) was 19.9±2.7 for progressed and 18.3±2.0 for nonprogressed patients (P<0.001). Progressed patients also showed a higher mean 24-h IOP. Generally, patients with a mean or peak daytime (readings at 10 A.M., 2 and 6 P.M.) or 24-h peak IOP of ≤18 remained nonprogressed in 75%-78% of cases. Further, measuring IOP at night found a higher peak in only 20% of cases, which was ≤2 of the daytime peak in 98% of cases. A multivariate regression analysis showed only 24-h peak IOP as an independent risk factor for progression (P=0.002). CONCLUSIONS This study suggests that daytime peak IOP may be clinically important in predicting long-term glaucomatous progression. Further, daytime peak IOP may assist, as much as daytime mean IOP and, in most cases, 24-h peak IOP, in helping to guide long-term treatment in POAG.

The effect of increased intraocular pressure on pulsatile ocular blood flow in low tension glaucoma

In the present study the relationship between intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) in low tension glaucoma (LTG) has been investigated. The POBF was measured using the Ocular Blood Flow system of Langham in undisturbed eyes and repeated at IOP increments of about 5 and 10 mmHg in 20 patients affected with bilateral LTG and in 25 healthy subjects matched for age, IOP, refractive error, arterial blood pressure and heart rate. The POBFs were 740.1 (SD 58.83) and 667 (SD 108) microliters/minute (microliter/min) in the control and LTG groups, respectively and statistically significantly different. The POBFs at an IOP increased by 5 mmHg were 658.1 (SD 60.2) and 457.3 (SD 74.8) microliter/min in the control and LTG groups, respectively; in the control group the mean POBF at an IOP increment of 10 mmHg was 552.1 microliters/min (SD 66.9), and in the LTG group was 317.7 microliters/min (SD 85.2). Statistical analysis of the data showed a significant difference of POBFs in the two groups either at an IOP increment of 5 or 10 mmHg (p < 0.0001). The substantial decrease of POBF with increased IOP in LTG eyes compared with normals shows an altered response of the vascular system in LTG. These findings are probably consistent with a lack of the myogenic autoregulation in reply to IOP-induced modifications of the perfusion pressure.

Twenty-four hour efficacy with preservative free tafluprost compared with latanoprost in patients with primary open angle glaucoma or ocular hypertension

Aim To compare 24 h intraocular pressure (IOP) control obtained with preservative free (PF) tafluprost 0.0015% versus branded preservative containing latanoprost 0.005% administered as first choice monotherapy in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT). Methods This prospective, observer-masked, crossover study included consecutive newly diagnosed patients with POAG or OHT, and baseline IOP between 24 and 33 mm Hg. Qualifying patients underwent baseline untreated 24 h IOP monitoring in habitual positions, with Goldmann tonometry at times 10:00, 14:00, 18:00 and 22:00, and Perkins supine tonometry at times 02:00 and 06:00. They were then randomised to either latanoprost or tafluprost, administered in the evening, for 3 months and then switched to the opposite therapy for another 3 months. 24 h monitoring was repeated at the end of each treatment period. Results 38 patients completed the study. Mean untreated 24 h IOP (24.9 mm Hg) was significantly reduced with both prostaglandins (p<0.001). Tafluprost demonstrated similar mean 24 h efficacy compared with latanoprost (17.8 vs 17.7 mm Hg; p=0.417). Latanoprost demonstrated significantly better 24 h trough IOP (15.9 vs 16.3 mm Hg; p=0.041) whereas tafluprost provided significantly lower 24 h IOP fluctuation (3.2 vs 3.8 mm Hg; p=0.008). No significant difference existed between the two prostaglandins for any adverse event. Conclusions PF tafluprost achieved similar 24 h IOP reduction to branded latanoprost. The current study highlights the importance of complete assessment of efficacy over 24 h. Clinical trials registration NCT01162603.

Twenty-four-hour intraocular pressure and blood pressure levels with bimatoprost versus latanoprost in patients with normal-tension glaucoma

Aim: To evaluate 24 h intraocular pressure (IOP) and blood pressure (BP) with bimatoprost or latanoprost in patients with normal-tension glaucoma. Design: Prospective, randomised, crossover, active-controlled, observer-masked study. Methods: After a 6-week medicine-free period, we randomised patients to either latanoprost or bimatoprost for 8 weeks and then to the opposite medicine for 8 weeks. At baseline, and at the end of each treatment period, we evaluated IOP and BP at 08:00 and then every 2 h over the 24 h day. Diastolic ocular perfusion pressure (DOPP) was calculated from the above parameters. Results: Forty completed patients had a 24 h untreated baseline IOP of 15.5 (2.3) mm Hg, and a DOPP of 59.2 (6.1) mm Hg. Both treatments lowered IOP at each time point (p<0.006), and over the 24 h curve (p<0.001, both medicines 13.1 mm Hg, 16% decrease). No difference existed between treatments in absolute IOP, at each time point, and over the 24 h curve (p⩾0.26). Additionally, no differences were found between treated 24 h systolic (p⩾0.29) and diastolic BP (p⩾0.12). The mean 24 h DOPP for latanoprost was increased from baseline (3%, p = 0.031) but not for bimatoprost (2%, p = 0.21). However, no difference in DOPP existed between treatments at any time point or over the 24 h curve (p⩾0.17). No difference was observed between treatments for any adverse event (p>0.05). Conclusions: In patients with normal-tension glaucoma, both bimatoprost and latanoprost reduce the 24 h intraocular pressure from untreated baseline to a similar extent. Latanoprost is associated with slightly improved ocular diastolic perfusion pressure over 24 h but similar absolute perfusion levels to that of bimatoprost.

Untreated 24-h intraocular pressures measured with Goldmann applanation tonometry vs nighttime supine pressures with Perkins applanation tonometry

AimsTo compare supine nighttime intraocular pressure measurements with Perkins applanation tonometry to 24-h sitting intraocular pressures with Goldmann applanation tonometry.MethodsA prospective, untreated, uncontrolled, observational cohort of qualified consecutive ocular hypertensive or primary open-angle glaucoma patients. Patients underwent sitting intraocular pressure measurements over 24-h by Goldmann and patients had their supine nighttime intraocular pressure measurements by Perkins.ResultsIn 100 completed patients, the mean intraocular pressure at 1000, 2200, 0200 and 0600 hours while sitting was 22.5±3.7 mm Hg, and in the supine position, 23.5±4.3 mm Hg (P<0.001). The mean sitting Goldmann intraocular pressures across the three daytime points was 23.3±3.4 mm Hg and across three nighttime points was 21.5±4.0 mm Hg (P<0.001). In contrast, the mean daytime sitting Goldmann intraocular pressure was not different than the mean nighttime supine intraocular pressure evaluated with Perkins (22.8±4.4 mm Hg, P=0.07). However, only 70% of patients were within 1.0 mm Hg of the highest daytime reading for all nighttime supine and sitting intraocular pressures.ConclusionThis study suggests that with Perkins applanation tonometry the untreated mean supine intraocular pressures are not higher at night than daytime sitting Goldmann applanation tonometry. However, the highest daytime sitting intraocular pressure measurement does not consistently predict the highest nighttime sitting or supine intraocular pressure value.