Ivano Riva

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.

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.

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.

Latanoprost ophthalmic solution in the treatment of open angle glaucoma or raised intraocular pressure: a review

Latanoprost is a prostaglandin F2-alpha isopropyl ester prodrug which is rapidly hydrolyzed by esterases in the cornea to the biologically active latanoprost acid. When latanoprost is topically administered into the eye, the cornea seems to act like as a slow-release depot to the anterior segment. One hour after administration maximum concentration is found in the iris, followed by the anterior chamber and the ciliary body. Despite extensive research, controversy remains about the real mechanism of action of this drug. Immunohistochemical data have shown that the intraocular pressure (IOP) reduction with topical prostaglandin F2-alpha is associated with a reduction of collagens within the uveoscleral outflow pathway. Evidence from several experimental and clinical studies suggests that latanoprost is a valuable addition first-line treatment alternatives for glaucoma, ocular hypertension and even angle-closure glaucoma. Strong points are its efficacy, which is demonstrated to be higher than that of brimonidine, dorzolamide and timolol with fewer systemic adverse effects; a convenient administration schedule; and the IOP-controlling pattern, which is relatively flat compared with timolol and dorzolamide, and enables better control in glaucoma progression, since large fluctuations may be associated with the risk of developing glaucoma in untreated ocular hypertensive subjects.

Quality of Life in Glaucoma: A Review of the Literature.

The ultimate goal of glaucoma management is the preservation of patients’ visual function and quality of life (QoL). The disease itself as well as the medical or surgical treatment can have an enormous impact on a patient’s QoL. Even the mere diagnosis of a chronic, irreversible, potentially blinding disorder can adversely affect the patient’s sense of well-being and QoL by eliciting significant anxiety. Patients with primary open-angle glaucoma rarely present with visual symptoms, at least early in the course of the disease. A better understanding of patient-reported QoL can improve patient–physician interaction and enhance treatment adherence by customizing treatment options based on individual patient profile, thus optimizing long-term prognosis. These aspects are summarized and critically appraised in this article.

Twenty-four hour efficacy with the dorzolamide/timolol-fixed combination compared with the brimonidine/timolol-fixed combination in primary open-angle glaucoma

AimThe aim of this study is to compare the 24-hour efficacy of dorzolamide/timolol-fixed combination (DTFC) and brimonidine/timolol-fixed combination (BTFC) in primary open-angle glaucoma (POAG).MethodsOne eye each of 77 POAG patients was included in this prospective, observer-masked, crossover comparison. Following a 2-month timolol run-in period, patients had three intraocular pressure (IOP) measurements at 1000, 1200 and 1400 h while on timolol treatment. Patients showing at least a 20% IOP reduction on timolol were randomised to 3 months of therapy with DTFC or BTFC, and then were crossed over to the opposite therapy.ResultsSixty POAG patients completed the study. The mean 24-hour IOP was significantly reduced with both the fixed combinations compared with the timolol-treated diurnal IOP (P<0.001). When the two fixed combinations were compared directly, DTFC demonstrated a lower mean 24-hour IOP level as compared with BTFC (mean difference: −0.7 mm Hg, 95% confidence interval (CI): (−1.0, −0.3), P<0.001). At two individual time points, DTFC significantly reduced IOP more than BTFC: at 1800 h (−1.0 mm Hg, 95% CI (−1.6,−0.5), P=0.001) and at 0200 (−0.9 mm Hg, 95% CI: (−1.4,−0.5), P=0.001). No significant difference existed for the other time points.ConclusionBoth the fixed combinations significantly reduce 24-hour IOP in POAG. DTFC provided significantly better 24-hour efficacy.

Circadian Intraocular Pressure and Blood Pressure Reduction With Timolol 0.5% Solution and Timogel 0.1% in Patients With Primary Open‐Angle Glaucoma

Purpose: To investigate the circadian and blood pressure (BP) reduction obtained with timolol maleate 0.5% solution administered twice daily versus timolol 0.1% in gel‐forming carbomer administered in the morning in patients with primary open‐angle glaucoma (POAG). Methods: This investigator‐masked, crossover study prospectively enrolled naive POAG patients not receiving systemic cardiovascular medications. Following a baseline evaluation, they were randomized to receive a timolol 0.5% solution or timolol 0.1% hydrogel for 2 months and then switched to the alternative medication for a further 2 months. Intraocular pressure (IOP) phasing (sitting Goldmann tonometry at 10 AM, 2 PM, 6 PM, and 10 PM and supine Perkins tonometry at 2 AM and 6 AM) and ambulatory home BP monitoring were measured at baseline and after each treatment period. Results: On the basis of a prospective sample size estimate, 28 patients were analyzed. Mean 24‐hour IOP decreased from 23.1 ± 0.7 mm Hg at baseline to 18.9 ± 0.6 mm Hg after timolol 0.5% and 18.9 ± 0.8 mm Hg after timolol 0.1% hydrogel (P < .001); both formulations also significantly decreased diurnal, nocturnal, and individual time point IOP in a statistically similar manner. Systolic and diastolic BP remained generally unaffected. The calculated diastolic ocular perfusion pressure was either unaffected or tended to increase with either medication. Conclusion: Both timolol formulations show similar and significant circadian efficacy and have minimal effects on BP and calculated diastolic ocular perfusion pressure.

Long-term 24-hour intraocular pressure control with travoprost monotherapy in patients with primary open-angle glaucoma.

Purpose:The aim of the study was to evaluate the long-term 24-hour intraocular pressure (IOP) efficacy of travoprost monotherapy in primary open-angle glaucoma patients. Patients and Methods:A total of 36 previously untreated primary open-angle glaucoma patients were enrolled in this 5-year study. Patients underwent an untreated 24-hour IOP evaluation. Subsequently all patients were assigned to topical therapy with travoprost 0.004% eye-drops preserved with benzalkonium chloride (Travatan, Alcon Laboratories Inc., Fort Worth, TX) administered once in the evening (8:00 PM) in both eyes. All patients were then scheduled for a 24-hour IOP assessment approximately 12 months after the baseline visit. This schedule of follow-up was maintained for the whole duration of the trial. The predetermined range of target IOP reduction selected in this cohort of patients ranged between 20% and 30%. Results:A total of 34 patients completed all phases of the investigation. The mean survival time was 57.3±2.0 months and the cumulative survival rate was 0.82±0.6 at 60 months. Travoprost reduced the mean 24-hour IOP from 23.4±1.7 mm Hg at baseline to 16.8±2.4 mm Hg (28.4%), 16.8±2.5 mm Hg (28.1%), 16.8±2.4 mm Hg (28.5%), 16.7±2.5 mm Hg (28.6%), and 16.9±2.4 mm Hg (27.8%), respectively at the end of the first, second, third, fourth, and fifth year follow-up. No drug-related serious adverse events were registered during the study. Conclusions:The present study demonstrated the long-term 24-hour efficacy of travoprost for the treatment of primary open-angle glaucoma.