Comparison of the effects of bimatoprost and a fixed combination of latanoprost and timolol on 24-hour blood and ocular perfusion pressures: the results of a randomized trial.

BACKGROUND: To compare the effect of bimatoprost and the fixed combination latanoprost-timolol (LTFC) on 24-hour systolic (SBP) and diastolic (DBP) blood pressure and on 24-hour ocular perfusion pressure (OPP). METHODS: 200 patients with glaucoma or ocular hypertension, controlled on the unfixed combination of latanoprost and timolol or eligible for dual therapy being not being fully controlled on monotherapy were enrolled in a randomized, double-masked, placebo-controlled, multicentre clinical trial. They were randomized to LTFC (8 a.m.) or bimatoprost (8 p.m.) and received 24-hour IOP curve at baseline, 6 and 12 weeks (supine and sitting position IOPs were recorded at 8 p.m., midnight, 5 a.m., 8a.m., noon and 4 p.m.). Holter 24-hour blood pressure curve was obtained between weeks 2 and 12. SBP, DBP, OPP were calculated and compared with ANOVA. Rates of diastolic OPP (DPP)≤50, ≤40, ≤30 mmHg in the 2 groups were calculated and compared using Fisher's test. RESULTS: Mean baseline SBP and DBP were 136.5±18.3 vs 134.2±20.1 mmHg (p=0.1) and 79.1±10.2 vs 78.2±10.1 mmHg (p=0.4) in the bimatoprost and LTFC groups respectively. Holter SBP was significantly higher for bimatoprost (135.1 mmHg vs 128.1 mmHg, p=0.04), while no statistically significant difference in DBP was found. DPP was similar in the 2 groups, and proportions of patients with at least one value of the 24-hour curve≤50, ≤40, ≤30 mmHg were 94%, 86%, 41% respectively. CONCLUSIONS: Bimatoprost and LTFC had similar DBPs and OPPs; SBP was significantly lower with LTFC. In this study, the percentage of "dippers" was considerably higher than the one described in previous studies on the role of perfusion pressure in glaucoma. TRIAL REGISTRATION: NCT02154217, May 21, 2014.

Effects of coenzyme Q10 in conjunction with vitamin E on retinal-evoked and cortical-evoked responses in patients with open-angle glaucoma.

PURPOSE: To evaluate pattern-evoked retinal and cortical responses [pattern electroretinogram (PERG) and visual-evoked potential (VEP), respectively] after treatment with coenzyme Q10 in conjunction with vitamin E in open-angle glaucoma (OAG) patients. METHODS: Forty-three OAG patients (mean age, 52.5±5.29 y; intraocular pressure <18 mm Hg with ß-blocker monoterapy only) were enrolled. At baseline and after 6 and 12 months, simultaneous recordings of PERG and VEPs were obtained from 22 OAG patients who underwent treatment consisting of coenzyme Q10 and vitamin E (Coqun, 2 drops/d) in addition to ß-blocker monoterapy (GC group), and from 21 OAG patients who were only treated with ß-blockers (GP group). RESULTS: At baseline, intraocular pressure, PERG, and VEP parameters were similar in both GC and GP groups (analysis of variance, P>0.05). After 6 and 12 months, PERG and VEP response parameters of GP patients were unchanged when compared to baseline. In GC patients, PERG P50 and VEP P100 implicit times were decreased, whereas PERG P50-N95 and VEP N75-P100 amplitudes were increased (P<0.01) when compared to baseline. In the GC group, the differences in implicit times and amplitudes with respect to baseline were significantly larger (P<0.01) than those recorded in the GP group. The improvement (12 mo minus baseline) of VEP implicit time was significantly correlated with the changes of PERG P50-N95 amplitude (r=-0.66171, P=0.0008) and P50 implicit time (r=0.68364, P=0.00045) over a period of 12 months. CONCLUSIONS: Coenzyme Q10 associated with vitamin E administration in OAG shows a beneficial effect on the inner retinal function (PERG improvement) with consequent enhancement of the visual cortical responses (VEP improvement).

An evaluation of therapeutic noninferiority of 0.005% latanoprost ophthalmic solution and xalatan in patients with glaucoma or ocular hypertension.

PURPOSE: To assess the therapeutic noninferiority of 0.005% latanoprost ophthalmic solution versus Xalatan in the treatment of patients with primary open-angle glaucoma or ocular hypertension. PATIENTS AND METHODS: This was a double-masked, randomized, multicenter study. A total of 184 patients with a diagnosis of unilateral or bilateral primary open-angle glaucoma or ocular hypertension were randomly assigned to either 0.005% latanoprost ophthalmic solution or Xalatan for 12 weeks. The primary end-point was the change in intraocular pressure (IOP) at 12 weeks in the 2 groups. Noninferiority was reached if the 2-sided 95% confidence intervals (CI) for the difference between adjusted treatment means were entirely within the interval from -1.5 to +1.5 mm Hg. RESULTS: The difference between treatments in the change of IOP from baseline to the end of treatment was 0.12 mm Hg (95% CI: -0.47, 0.71) in the intention-to-treat population and 0 mm Hg (95% CI: -0.58, 0.57) in the per protocol population. There was no statistically significant difference between the 2 groups in terms of drug-related adverse events. The most commonly reported drug-related local adverse events were: ocular hyperemia, eyelashes growth, and eye irritation. CONCLUSIONS: This study demonstrates that 0.005% latanoprost ophthalmic solution is noninferior to Xalatan in lowering IOP and is generally well tolerated.

Acute stroke after intravitreal bevacizumab to treat choroidal neovascularization due to angioid streaks in pseudoxanthoma elasticum : a severe systemic adverse event after an off-label procedure.

To report the occurrence of acute stroke after intravitreal bevacizumab administration to treat choroidal neovascularization due to angioid streaks in a patient affected by pseudoxanthoma elasticum. A 54-year-old man with pseudoxanthoma elasticum had vision loss because of choroidal neovascularization due to angioid streaks. He underwent two intravitreal bevacizumab injections. Three days after the second procedure the patient was afflicted by acute stroke. Intravitreal injection of bevacizumab to treat choroidal neovascularization due to angioid streaks in pseudoxanthoma elasticum could lead to severe systemic adverse events.

Oral administration of forskolin and rutin contributes to intraocular pressure control in primary open angle glaucoma patients under maximum tolerated medical therapy.

BACKGROUND: Tight control of intraocular pressure (IOP) is still the only therapeutic approach available for the treatment of primary open angle glaucoma (POAG). However, some patients do not respond adequately to hypotonising drugs, and despite multiple drug combinations they cannot reach their target IOP. Forskolin is a natural compound that has already shown efficacy in IOP reduction following topical application. PURPOSE: The aim of this study was to evaluate the effects on the IOP of a food supplement containing forskolin and rutin when administered to POAG patients under maximum tolerated medical therapy (MTMT) and on a waiting list for filtrating surgery to further decrease their IOP. METHODS: The design of the study was open and case-controlled. Ninety-seven (52 in the treatment group, and 45 in the reference group) patients were enrolled in 8 different glaucoma centers in Italy, all under MTMT and with IOP enrollment values above their target pressure. During the 30 days before surgery, patients in the treatment group were prescribed 2 tablets per day of a food supplement containing rutin and forskolin in addition to their usual topical drug treatment. Their IOP values were measured at 3 time points during the day, at enrollment and once a week until surgery. Control patients continued only with their normal topical therapy. RESULTS: All patients in the treatment group, independently of the combination drug therapy that they were taking, showed a further 10% decrease (P<0.01) of their IOP, starting from 1 week after introduction of the oral supplement and lasting until the last evaluation before surgery. This decrease was more evident (15% of the enrollment value; P<0.01) in those subjects with high (IOP≥21 mmHg) enrollment values rather than in those with low (IOP<21) enrollment values (9%; P<0.01). On the contrary, IOP values in the control group remained stable from the beginning to the end of the observation period, independently of their enrollment values. CONCLUSIONS: Forskolin and rutin given as oral treatment appear to contribute to a better control and a further small reduction of IOP in patients who were poorly responsive to multitherapy treatment.

Bilateral progressive visual loss in an epileptic, mentally retarded boy.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited, monosymptomatic disorder, characterized by severe central vision loss and optic atrophy that most frequently affects young men. The classic LHON phenotype is associated to three mitochondrial DNA mutations, mostly homoplasmic, in the Mt-ND4, Mt-ND6, and Mt-ND1 genes, encoding for complex I subunits of the mitochondrial respiratory chain. Rare cases have been described in the literature in association with variable central nervous system involvement in a syndromic form called LHON 'plus.' In the present study, we report the case of a 16-year-old boy with the 3460/ND1 mutation who presented with epilepsy, migraine, and mental retardation as non-ophthalmic features. We also investigated his relatives who all had the 3460/ND1 mutation.

A case of sympathetic ophthalmia after a severe acanthamoeba keratitis.

PURPOSE: To report a case of sympathetic ophthalmia (SO) after a severe Acanthamoeba keratitis. METHODS/DESIGN: Interventional case report. RESULTS: A 59-year-old white woman, wearing contact lenses, developed a severe Acanthamoeba keratitis in the left eye, which involved the limbus, and required 8 months of intensive antiamoeba therapy; the condition resolved leaving a painful, phthisical eye with complete corneal neovascularization. Six months later, the patient presented with pain, blurred vision, and photophobia in the right eye. Slitlamp examination of the right eye revealed granulomatous uveitis. On the suspicion of an SO, treatment with high-dose topical and oral corticosteroids and immunosuppressants was started. After 3 months, the eye is stable, with a visual acuity of 20/50, and the patient is taking prednisolone 7.5 mg per day and cyclophosphamide 50 mg per day. CONCLUSIONS: [corrected] Development of SO in the absence of previous trauma or surgery is rare. Our case is the first report of a clinically diagnosed SO after an episode of severe Acanthamoeba keratitis.

Surgical reposition of a dislocated Ex-PRESS miniature device.

PURPOSE: To present a technique of surgical reposition of the Ex-PRESS miniature glaucoma device when dislocated in corneal limbus. METHODS: A 54-year-old woman diagnosed with glaucoma, with a 3-month history of Ex-PRESS miniature implant, was referred to our department because of progressive intraocular pressure (IOP) rise. Slit-lamp biomicroscopy showed the posterior flange of the implant located in the corneal limbus; IOP was 34 mmHg. Surgical technique consisted of reopening of the conjunctiva and the scleral flap, excision of the corneal tissue covering the flange, and stitching the implant to the sclera with polyprolene suture. RESULTS: Postoperatively, IOP rapidly reduced to 5 mmHg and was balanced to 10 mmHg in the follow-up. CONCLUSIONS: Corneal dislocation of the Ex-PRESS implant, when associated with ocular hypertension, needs surgical treatment. Before considering a trabeculectomy, it could be valuable to attempt an implant reposition.

Transient myopic shift as the presenting symptom of systemic lupus erythematosus: a UBM study.

PURPOSE: To report ultrabiomicroscopy (UBM) evidence of choroid effusion as a cause of acute transient myopia in the onset of systemic lupus erythematosus. DESIGN: Observational case report. METHODS: A Caucasian 16-year-old girl was referred to the Hematology Department for progressive anemia, intermittent fever, and blurred vision. RESULTS: Systemic lupus erythematosus was confirmed by hematological investigations. UBM examination evidenced choroid effusion as the cause of a transient myopic shift. CONCLUSIONS: Early diagnosis, thanks to the performance of an ultrasound examination, enabled the timely institution of therapy and hence a rapid resolution of the symptoms.

Ex-PRESS miniature glaucoma device in vitrectomized eyes.

PURPOSE: To evaluate the clinical efficacy and safety of the Ex-PRESS miniature glaucoma device placed under scleral flap for the treatment of ocular hypertension in eyes that underwent vitreoretinal surgery. METHODS: Vitrectomized patients who required glaucoma surgery for persistent ocular hypertension were included. The Ex-PRESS miniature glaucoma device was implanted under scleral flap. Postsurgical clinical outcomes and intraocular pressure (IOP) was monitored for 6 months after surgery. RESULTS: At 6 months, all the patients had an IOP lower than 18 mmHg, 3 of them without topical therapy. CONCLUSIONS: The use of the Ex-PRESS implant under scleral flap in eyes that underwent vitreoretinal surgery was effective for lowering IOP.

Bilateral sixth nerve palsy as a manifestation of Wernicke's encephalopathy in a patient with refractory vomiting.

PURPOSE: To report a case of Wernicke's encephalopathy in a nonalcoholic woman with secondary hypoadrenalism. METHODS: A 58-year-old Italian woman developed Wernicke's syndrome secondary to recurrent vomiting due to secondary hypoadrenalism. RESULTS: Recurrent vomiting and resulting malnutrition caused a depletion of the patient's body stores of thiamine and the development of mental confusion and an oculomotor deficit. On the diagnostic suspicion of encephalitis in this patient with immunosuppression due to prolonged cortisone-based therapy, she underwent magnetic resonance imaging, which showed typical bilateral abnormal lesions pathognomonic of Wernicke's encephalopathy. The patient improved after parenteral administration of vitamin B1. CONCLUSIONS: Wernicke's encephalopathy must be regarded as a medical emergency that should be suspected in all cases presenting with a sudden deficit or lack of coordination of the ocular movements associated with ataxia and general degeneration of the mental faculties, in patients who have suffered recurrent vomiting or malnutrition for different reasons.

Primary open angle glaucoma: an overview on medical therapy.

The purpose of this review is to discuss the topics relevant to the use of intraocular pressure-lowering strategies, which remains the first line in the management of glaucoma. Estimates of blindness from glaucoma and identification of risk factors remain of interest for all ophthalmologists. New functional tests offer promise for better detection and more accurate diagnosis of glaucoma. We finally discuss the impact of various glaucoma therapies, the principles of monotherapy and fixed combinations, which offer benefits of convenience, cost, and safety.

Learning effect of humphrey matrix frequency doubling technology perimetry in patients with ocular hypertension.

AIM: To evaluate the learning effect of Frequency Doubling Technology (FDT) perimetry using the Humphrey Matrix-FDT perimetry (Matrix) 24-2 full-threshold program on patients with ocular hypertension experienced with standard automated perimetry. METHODS: Twenty-four patients with ocular hypertension underwent 5 full-threshold Matrix tests at intervals of 5+/-2 days. Learning effect was defined as an improvement at results for duration, perimetric indices, foveal sensitivity, Glaucoma Hemifield Test, and the number of points with a P<5% and <1% in the total and pattern deviation maps. Eccentricity, hemifield, and quadrant sensitivities were also addressed as sources of differences in learning effect. Test-retest variability was also calculated for each repetition as the mean of the point-to-point interindividual standard deviations. RESULTS: A learning effect was demonstrated for mean defect (P=0.031, analysis of variance) and foveal sensitivity (P=0.009) and it only affected the first test for both parameters. All the other parameters did not show any significant learning effect. The effect was independent from eccentricity and quadrant or hemifield sensitivities. CONCLUSIONS: The results of this study demonstrate that the learning effect for Matrix-FDT is mild and it may affect only the first test. Caution is needed in the analysis of the first Matrix-FDT examination and retest may be advisable in the presence of low mean defect.

The role of antimetabolites in filtration surgery for neovascular glaucoma: intermediate-term follow-up.

PURPOSE: To compare the intermediate-term efficacy of 5-fluorouracil (5-FU) and Mitomycin C (MMC) as adjunctive antimetabolites in neovascular glaucoma (NVG) filtration surgery. METHODS: Forty consecutive eyes of 40 patients with NVG refractory to medical therapy were randomized to receive antimetabolite-augmented trabeculectomy. Eighteen eyes received postoperative 5-FU (5-FU group) and 22 eyes received intraoperative, low-dose (0.2 mg/ml) MMC for 2 mins (MMC group). The main outcome measure was intraocular pressure (IOP). Surgical success was defined as IOP < 21 mmHg with topical treatment (qualified success) or without topical treatment (complete success). Surgical failure was defined as IOP > or = 21 mmHg, despite postoperative topical treatment, and by postoperative blindness. RESULTS: The mean follow-up period was 35.8 +/- 22.6 months in the 5-FU group and 18.6 +/- 17.2 months in the MMC group. This difference was not significant. Mean IOP decreased from 40.4 +/- 10.3 mmHg to 14.7 +/- 3.4 mmHg (p < 0.0001) in the 5-FU group and from 42 +/- 11.3 mmHg to 22.9 +/- 13.3 mmHg (p = 0.0006) in the MMC group; however, the difference between the 5-FU and MMC groups was not significant at any point. The success rate in the 5-FU group was 55.5% (44.4% complete, 11.1% qualified), compared with 54.5% (9.1% complete, 45.4% qualified) in the MMC group. This difference was not significant. CONCLUSIONS: The percentage of patients who achieved postoperative IOP < 21 mmHg was similar in both groups, although a larger proportion of patients treated with MMC-augmented trabeculectomy required topical treatment in comparison with the 5-FU group.

Comparison of the effects of bimatoprost and a fixed combination of latanoprost and timolol on circadian intraocular pressure.

OBJECTIVE: To compare the effect of bimatoprost and the fixed combination of latanoprost and timolol (LTFC) on 24-hour mean intraocular pressure (IOP) after patients are switched from a nonfixed combination of latanoprost and timolol. DESIGN: Randomized, double-masked, multicenter clinical trial. PARTICIPANTS: Two hundred patients with glaucoma or ocular hypertension. METHODS: Included were patients who were controlled (IOP < 21 mmHg) on the nonfixed combination of latanoprost and timolol for at least 3 months before the baseline visit or patients on monotherapy with either latanoprost or timolol who were eligible for dual therapy not being fully controlled on monotherapy. The latter group of patients underwent a 6-week wash-in phase with the nonfixed combination of latanoprost and timolol before baseline IOP determination and study inclusion. Supine and sitting position IOPs were recorded at 8 pm, midnight, 5 am, 8 am, noon, and 4 pm at baseline, week 6, and week 12 visits. MAIN OUTCOME MEASURE: An analysis of covariance model was used for a noninferiority test of the primary efficacy variable, with mean area under the 24-hour IOP curve after 12 weeks of treatment as response variable and treatment, center, and baseline IOP as factors. A secondary analysis was performed on the within-treatment change from baseline. RESULTS: Mean baseline IOPs were 16.3+/-3.3 mmHg and 15.5+/-2.9.mmHg in the bimatoprost and LTFC groups, respectively. At week 12, mean IOPs were 16.1+/-2.5 mmHg for the bimatoprost group and 16.3+/-3.7 mmHg for the LTFC group, and no significant difference between the 2 treatment groups could be found. As compared with baseline, mean IOP increased by 0.3+/-3.6 mmHg during the day and decreased by 0.8+/-3.8 mmHg during the night in the bimatoprost group, whereas there were increases of 1.43+/-2.6 mmHg and 0.14+/-3.2 mmHg in the LTFC group, respectively. CONCLUSIONS: Bimatoprost is not inferior to the LTFC in maintaining IOP at a controlled level during a 24-hour period in patients switched from the nonfixed combination of latanoprost and timolol.

The influence of low to moderate myopia on retinal nerve fiber layer as assessed by scanning laser polarimetry with variable corneal compensator.

PURPOSE: To evaluate the influence of different degrees of myopia on retinal nerve fiber layer (RNFL) as measured by scanning laser polarimetry (SLP) with variable corneal compensator (VCC) in healthy eyes. METHODS: One hundred and seventy-four healthy age-matched subjects with low to high myopic and emmetropic eyes underwent RNFL measurement by means of GDxVCC. The GDx parameters included in the analysis were: Temporal-superior-nasal-inferior thickness (TSNIT) average, Superior average, Inferior average, TSNIT standard deviation, Inter-eye symmetry, NFI, Symmetry, Superior ratio, Inferior ratio, Superior/nasal, Maximum modulation, Superior maximum, Inferior maximum, Ellipse modulation, Normalized superior area, Normalized inferior area, Ellipse standard deviation, Ellipse average. The mean value of each SLP parameter of myopic eyes was compared with the mean value of the same parameter of emmetropic eyes. RESULTS: Mean myopia was 3.9 +/- 1.5 dpt (range: -2 to -8.25 dpt). TNSIT average was higher in myopic group (p = 0.0111), together with Superior average (p = 0.0244), Symmetry (p < 0.0001) and Ellipse average (p = 0.0111). Two ratio parameters, Superior ratio and Inferior ratio, were higher in emmetropic eyes (p = 0.0179 in both cases). In both the myopic and the emmetropic group, all the SLP assessments of the RNFL fell within the normal range, according to the GDx database. CONCLUSIONS: Low to high myopia is not related to clinically relevant variations of SLP parameters, as assessed with GDx-VCC.

Learning effect of short-wavelength automated perimetry in patients with ocular hypertension.

AIM: To evaluate the learning effect of short-wavelength automated perimetry (SWAP) on a group of patients with ocular hypertension experienced with standard automated perimetry (SAP). METHODS: Thirty patients with ocular hypertension underwent 5 full-threshold SWAP tests at intervals of 7+/-2 days. The parameters investigated to detect a learning effect were duration, the perimetric indices, and the number of points with a P of <5% and 1% in the total and pattern deviation maps. Differences in learning effect were also evaluated by comparing the sensitivities of central, paracentral, and peripheral areas, hemifields and quadrants. RESULTS: Learning effects were demonstrated for mean defect (P<0.0001, analysis of variance), duration (P=0.0001), the number of points with P<5% in the pattern deviation map (P=0.003), and short fluctuations (P=0.03). The effect was greater in the peripheral than in central areas (P=0.04). Mean defect was the most sensitive parameter, for which the learning effect was statistically significant between the first and the fifth test. CONCLUSIONS: The results of this study demonstrate a significant learning effect at full-threshold SWAP. This may limit the efficacy of this kind of perimetry in detecting early glaucoma, and should therefore be carefully considered when creating normative databases for new SWAP strategies.

Is there still a clinical use for scanning laser polarimetry with fixed corneal compensator?

PURPOSE: To compare the scanning laser polarimetry device with a fixed corneal compensator (GDx FCC) with the new version with a variable corneal compensator (GDx VCC) in healthy subjects. METHODS: A prospective, nonrandomized, comparative trial was carried out with both the FCC and the VCC systems on 130 healthy volunteers. The FCC measurements were divided into 2 subgroups, in accordance with the appearance of the macula. Subjects with a uniform aspect of the macula were included in the macula-'negative' group (macula-), whereas subjects with an irregular macular appearance with FCC were included in the macula-'positive' group (macula+). Data relative to all the GDx parameters were examined. For each parameter, we compared the data obtained by the FCC to the VCC models. Subsequently we compared each FCC subgroup (macula+ and macula-) to VCC. RESULTS: A total of 67 subjects entered the macula- group and 63 the macula+ group. FCC significantly overestimated the average parameters and underestimated the number, the modulation and also the ratio parameters. The only parameter showing no difference was symmetry. Similar trends were also evident when the subjects were divided into the macula+ and - subgroups. CONCLUSION: Individual variations of corneal birefringence, which are not completely corrected by FCC, result in over- or underestimation of retinal nerve fiber layer parameters. This measurement error cannot be eliminated, not even by only selecting patients with a uniform aspect of macular scan. For this reason GDx FCC does not seem to be an acceptable tool in the early diagnosis of glaucoma, and modern versions of this device should be preferred.

Red blood cell (RBC) surface acetylcholinesterase showing a hemorheological pattern during glaucoma treatment.

BACKGROUND: Glaucoma is currently attributed to two different possible pathogenetic mechanisms: mechanical (the ocular damage is induced by physical injury), and vascular (the ocular damage is sustained by ischemia of the optic nerve head). AIM: We considered the possibility that several anti-glaucoma drugs (beta-blockers, carbonic anhydrase inhibitors and prostaglandins) could have an influence on optic nerve head hemorheology and oxygen supply. MATERIALS AND METHOD: We studied 4 groups of 10 subjects each: a control group, and 3 primary open angle glaucoma (POAG) groups, treated with topical beta-blockers, (10 patients), carbonic anhydrase inhibitors (CAI), and prostaglandin analogs (PG), respectively. In these 4 groups we investigated the RBC surface AchE and cytosolic calcium levels in order to assess their possible influence on the hemorheology and microcirculation in optic nerve head blood perfusion. RESULTS: A significant correlation (p < 0.048) was found between the RBC surface acetylcholinesterase and RBC intracytosolic calcium values in patients with POAG treated with beta-blockers. We found no significant correlation (p = n.s.) between the same patterns in the other Groups or in Controls. CONCLUSION: These data indicate that CAI and PG drugs do not interfere with AchE in POAG patients, whereas beta-blockers negatively affect the RBC deformability.