Levobetaxolol hydrochloride: a review of its pharmacology and use in the treatment of chronic open-angle glaucoma and ocular hypertension

Levobetaxolol is a cardioselective β-blocker that has been demonstrated to reduce intraocular pressure in patients affected with primary open-angle glaucoma and ocular hypertension. Levobetaxolol may be an effective neuroprotectant because of its great capacity to block sodium and calcium influx, which might confer a neuroprotective activity. Experimental and clinical studies have demonstrated the effects of levobetaxolol on ocular hemodynamics and visual field, and the pharmacologic differences between β-blockers currently used for the treatment of elevated IOP have become of more than academic interest since a number of studies have shown improvements to various extents. Unlike the initially manufactured 0.5% ophthalmic solution, levobetaxolol is suspended in a different delivery vehicle in levobetaxolol ophthalmic suspension, to increase the ocular tolerance and allow a similarity of effect with a 2-fold reduced concentration (0.25%)

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Arteriolar Diameters in Glaucomatous Eyes with Single-Hemifield Damage

PURPOSE: To examine the association between retinal arteriolar caliber and lumen, retinal sensitivity (RS), and retinal nerve fiber layer (RNFL) thickness in glaucomatous eyes with single-hemifield loss. METHODS: We conducted a prospective, nonrandomized, case-control study of 20 eyes of 20 patients with glaucoma with visual field damage confined to a single hemifield. The control group was composed of 20 eyes of 20 normal subjects. For all the eyes, we performed optical coherence tomography to assess the RNFL and standard automated perimetry to evaluate RS. External and internal arteriolar diameters were assessed in vivo using scanning laser Doppler flowmetry. RESULTS: The RNFL was significantly thinner in glaucomatous eyes than in normal eyes (p < 0.001). In glaucomatous eyes, a positive correlation between sectorial RNFL thickness and the corresponding external and internal arteriolar diameters was found (r = 0.43, p = 0.05; r = 0.63, p = 0.003, respectively). The internal arteriolar diameter significantly correlated with RS in the corresponding abnormal hemifield (r = 0.44, p = 0.04). Compared with the normal hemifield, the internal arteriolar diameter, RNFL thickness, and RS were significantly reduced, whereas the external arteriolar diameter was unchanged in the abnormal hemifield. CONCLUSIONS: In glaucomatous eyes with single-hemifield damage, attenuation of retinal vessels was associated with a thinner RNFL and reduced RS. Moreover, a narrower lumen with increased wall-to-lumen ratio was found in the abnormal hemifield, supporting the hypothesis that vessel narrowing is likely secondary to a lower demand for blood flow in the glaucomatous areas of the retina

Twelve-month results of treatment with intravitreal ranibizumab, intravitreal ranibizumab plus ketorolac eye drops, and intravitreal ranibizumab plus low-fluence photodynamic therapy for exudative age-related macular degeneration

Purpose To compare the effectiveness of treatment with intravitreal ranibizumab (IVR), IVR plus ketorolac eye drops, and IVR plus low-fluence photodynamic therapy (PDT) for choroidal neovascularization (CNV). Methods This was a multicenter, prospective, pilot study of eyes with new-onset CNV. Seventy-five eyes were enrolled consecutively and randomized to one of 3 groups at a ratio of 1:1:1. Group 1 (n = 25) received IVR; Group 2 (n = 25) received IVR along with topical ketorolac eye drops 3 times a day; while Group 3 (n = 25) received 1 session of low-fluence PDT followed by IVR. In all groups, ranibizumab 0.5 mg was injected monthly for 3 months, and then as needed in accordance with the standard of care. All patients were followed up for 12 months. Results At 12 months, all groups showed significant improvements in best-corrected visual acuity (BCVA; p < 0.001). Group 2 showed a greater mean 12-month BCVA improvement than both groups 1 and 3 (p = 0.049 and p = 0.039, respectively). The mean 12-month change in central macular thickness (CMT) was -131 µm (-29.4%; p < 0.001) in Group 1, -138 µm (-33.4%; p < 0.001) in Group 2, and -129 µm (-29.5%; p < 0.001) in Group 3. Group 2 showed a greater mean CMT reduction than both Groups 1 and 3 (p = 0.002 and p = 0.014, respectively), while anatomical improvements were similar between Groups 1 and 3. None of the 3 groups showed any adverse effects. Conclusions This is the first study to report better BCVA outcomes over a 12-month period with a combination of 0.45% ketorolac eye drops 3 times a day and IVR in patients with CNV, further indicating that topical ketorolac supplements the CMT-reducing activity of IVR in CNV. A combination therapy of PDT plus ranibizumab injections did not yield anatomical or functional improvements; however, fewer ranibizumab injections were required. Larger trials are needed to confirm the findings of this pilot study

Combination of ranibizumab and indomethacin for neovascular age-related macular degeneration: randomized controlled trial

Purpose: The aim of this study was to evaluate whether indomethacin eye drops and intravitreal ranibizumab (IVR) injections would provide additional benefit over ranibizumab alone in the treatment of choroidal neovascularization (CNV). Participants and methods: This was a randomized, prospective pilot study of eyes with new-onset CNV. Fifty-eight patients were randomized 1:1 into a ranibizumab monotherapy (RM) group and a ranibizumab plus indomethacin (RI) group. All patients received monthly 0.5 mg IVR injections for 3 months, followed by monthly injections administered as needed. RI group patients also self-administered one drop of 0.5% indomethacin three times a day for 12 months. All patients were followed up for 12 months. Results: At 12 months, both groups showed significant improvement in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). The mean BCVA change from baseline to 12 months was −0.12±0.04 LogMAR and −0.20±0.04 LogMAR in the RM and RI groups, respectively, with the degree of change being significantly different between the two groups (P=0.04). At 12 months, the mean CRT in the RM group (316±41.2 μm) was significantly higher than that in the RI group (287±31.5 μm; P=0.004). The mean required number of IVR injections was 7.38±0.78 and 6.34±0.67 in the RM and RI groups, respectively (P,0.001). Conclusion: Compared to IVR monotherapy, combination therapy with indomethacin eye drops and IVR provides superior anatomical and visual outcomes in patients with naive CNV lesions. Moreover, topical indomethacin might reduce the frequency of IVR injections, which is very beneficial considering the chronic and expensive nature of IVR therapy

Combination of ranibizumab and indomethacin for neovascular age-related macular degeneration: randomized controlled trial

Purpose: The aim of this study was to evaluate whether indomethacin eye drops and intravitreal ranibizumab (IVR) injections would provide additional benefit over ranibizumab alone in the treatment of choroidal neovascularization (CNV). Participants and methods: This was a randomized, prospective pilot study of eyes with new-onset CNV. Fifty-eight patients were randomized 1:1 into a ranibizumab monotherapy (RM) group and a ranibizumab plus indomethacin (RI) group. All patients received monthly 0.5 mg IVR injections for 3 months, followed by monthly injections administered as needed. RI group patients also self-administered one drop of 0.5% indomethacin three times a day for 12 months. All patients were followed up for 12 months. Results: At 12 months, both groups showed significant improvement in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). The mean BCVA change from baseline to 12 months was −0.12±0.04 LogMAR and −0.20±0.04 LogMAR in the RM and RI groups, respectively, with the degree of change being significantly different between the two groups (P=0.04). At 12 months, the mean CRT in the RM group (316±41.2 μm) was significantly higher than that in the RI group (287±31.5 μm; P=0.004). The mean required number of IVR injections was 7.38±0.78 and 6.34±0.67 in the RM and RI groups, respectively (P,0.001). Conclusion: Compared to IVR monotherapy, combination therapy with indomethacin eye drops and IVR provides superior anatomical and visual outcomes in patients with naive CNV lesions. Moreover, topical indomethacin might reduce the frequency of IVR injections, which is very beneficial considering the chronic and expensive nature of IVR therapy