Andreas Katsanos

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.

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.

Cerebral sinus venous thrombosis in inflammatory bowel diseases

BACKGROUND It has been estimated that 1.3-6.4% of patients with inflammatory bowel diseases (IBD) are complicated by cerebral venous thrombosis (CVT) at some point of time during the course of their disease. METHODS We retrospectively reviewed and subsequently analyzed data from 65 case reports of IBD patients with CVT. Our sources included MEDLINE and EMBASE, and the references of retrieved articles were also screened. RESULTS Patients with CVT and IBD were significantly younger than CVT patients without IBD. Female patients were complicated more frequently but at an older age when compared with males. The incidence of ulcerative colitis was almost double compared with Crohns disease. Active disease was detected in 78.4% of the cases and the proportions of patients with active ulcerative colitis or active Crohns disease were almost equal. The predominant neurological symptom in these patients was persistent headache (80%) and the most common site of CVT was the superior sagittal sinus (50.7%). Severe iron deficiency anemia was highlighted as a significant risk factor for thrombosis in nearly half of the patients. Transient coagulation abnormalities and hereditary thrombogenic mutations were identified in 23 and 20% of the case reports, respectively. CONCLUSION The overall outcome was very good, especially in those patients who were treated acutely with heparin or low molecular weight heparin, suggesting that heparin administration is related with improved neurological outcome and decreased mortality rates even in IBD patients complicated with CVT.

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.

Effect of trabeculectomy and canaloplasty on intra-ocular pressure modifications after postural changes in open-angle glaucoma.

haemorrhage. Nine subjects presented recurrent subretinal haemorrhage during the follow-up period. As these new haemorrhages all developed more than 1 week postoperatively, they were likely caused by the underlying disease rather than the intervention. This study is limited by its noncomparative, non-randomized retrospective design and relatively short-term follow-up. The timing of the final follow-up visit was highly variable. Consequently, the results from the final followup are highly comparable to the results at 6 weeks (median: 55 days). The lack of a control group is another limitation of this study. However, our results compare favourably to those of other similar studies evaluating the natural course of submacular haemorrhage. A prospective case series by Cheung et al. (2013). indicated amedian improvement in VA of 0.20 LogMAR units after 6 months. Similarly, retrospective data collection of 86 eyes revealed a 10.5%VA improvement after 6 months (Chen et al. 1999). In summary, the results of this study indicate that our surgical approach may be an effective treatment for submacular haemorrhage displacement in AMD patients. The procedure improved the visual recovery. However, the visual outcome is limited by the underlying macular pathology. Larger multicentre randomized controlled studies are warranted to determine the therapeutic effect of this surgical approach.

24-h Efficacy of Glaucoma Treatment Options

Current management of glaucoma entails the medical, laser, or surgical reduction of intraocular pressure (IOP) to a predetermined level of target IOP, which is commensurate with either stability or delayed progression of visual loss. In the published literature, the hypothesis is often made that IOP control implies a single IOP measurement over time. Although the follow-up of glaucoma patients with single IOP measurements is quick and convenient, such measurements often do not adequately reflect the untreated IOP characteristics, or indeed the quality of treated IOP control during the 24-h cycle. Since glaucoma is a 24-h disease and the damaging effect of elevated IOP is continuous, it is logical that we should aim to understand the efficacy of all treatment options throughout the 24-h period. This article first reviews the concept and value of diurnal and 24-h IOP monitoring. It then critically evaluates selected available evidence on the 24-h efficacy of medical, laser and surgical therapy options. During the past decade several controlled trials have significantly enhanced our understanding on the 24-h efficacy of all glaucoma therapy options. Nevertheless, more long-term evidence is needed to better evaluate the 24-h efficacy of glaucoma therapy and the precise impact of IOP characteristics on glaucomatous progression and visual prognosis.

Twenty-four hour efficacy of glaucoma medications.

Current medical therapy of glaucoma aims to attain a meaningful and consistent reduction of intraocular pressure (IOP) to a predetermined level of target IOP, which will commensurate with either stability, or delayed progression of visual loss. Glaucoma is a 24-h disease and the damaging effect of elevated IOP is continuous. Therefore, it is reasonable that we should endeavor to identify the true efficacy of currently available and future antiglaucoma medications throughout the 24-h period. This review chapter deals first with the concept and value of diurnal and 24-h pressure monitoring. It then evaluates existing evidence on the 24-h efficacy of medical therapy options. Unfortunately, significant gaps exist in our present understanding of the short-term and particularly the long-term 24-h efficacy of most antiglaucoma medications. More long-term controlled evidence is needed in the future to improve our understanding of the 24-h efficacy of current medical glaucoma therapy, the ideal 24-h target pressure and the precise impact of IOP characteristics upon the different stages of the various forms of glaucoma.

Management of exfoliative glaucoma: challenges and solutions

Exfoliative glaucoma is the most common type of secondary open-angle glaucoma worldwide. It is characterized by high intraocular pressure (IOP) and worse 24-hour IOP characteristics. In order to minimize progression, treatment of exfoliative glaucoma has to provide a low long-term mean IOP and good 24-hour IOP control. To achieve these goals, fixed-dose combination eye drops, argon and selective laser trabeculoplasty, and various forms of surgery (trabeculectomy, deep sclerectomy, viscocanalostomy, ab interno trabeculotomy, trabecular aspiration, and cataract surgery) all need to be considered during the long-term management of the disease. Since exfoliative glaucoma is a disease of the elderly, and is frequently associated with systemic vascular disease, interdisciplinary consultations are of great clinical importance. These management aspects and the current medical, laser, and surgical results are covered in this review, with a special focus on the needs of the general ophthalmologist.