Treatment of Open-Angle Glaucoma and Ocular Hypertension with the Fixed-Dose Combination of Preservative-Free Tafluprost/Timolol: Clinical Outcomes from Ophthalmology Clinics in Italy.

Introduction: The VISIONARY study examined the intraocular pressure (IOP)-lowering efficacy and tolerability of the preservative-free fixed-dose combination of tafluprost (0.0015%) and timolol (0.5%) (PF tafluprost/timolol FC) in a real-world setting. The country-level data reported herein comprise the largest and first observational study of PF tafluprost/timolol FC therapy in Italy. Methods: An observational, multicenter, prospective study included adult Italian patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) demonstrating insufficient response or poor tolerability with topical prostaglandin analogue (PGA) or beta-blocker monotherapy. Treatment was switched to PF tafluprost/timolol FC therapy at baseline. Primary endpoint was the absolute mean IOP change from baseline at Month 6. Exploratory and safety endpoints included change in IOP at Weeks 4 and 12, ocular signs, symptom severity and reporting of adverse events (AEs). Results: Overall, 160 OAG/OHT patients were included. Mean ± standard deviation IOP was reduced from 19.6 ± 3.6 mmHg at baseline to 14.5 ± 2.6 mmHg at Month 6 (reduction of 5.1 ± 3.7 mmHg; 24.1%; p < 0.0001). IOP reduction was also statistically significant at Week 4 (23.1%; p < 0.0001) and Week 12 (24.7%; p < 0.0001). Based on data cutoff values for mean IOP change of ≥20%, ≥25%, ≥30% and ≥35%, respective Month 6 responder rates were 68.1%, 48.7%, 36.2% and 26.9%. Most ocular signs and symptoms were significantly reduced in severity from baseline at Month 6. Two non-serious and mild AEs were reported during the study period, among which, one AE was treatment-related (eyelash growth). . Conclusion: Italian OAG and OHT patients demonstrated a significant IOP reduction from baseline at Week 4 that was maintained over a 6-month period following a switch from topical PGA or beta-blocker monotherapy to PF tafluprost/timolol FC therapy. Severity of most ocular signs and symptoms was significantly reduced during the study period, and PF tafluprost/timolol FC was generally well tolerated.

Pattern Electroretinogram Detects Localized Glaucoma Defects.

PURPOSE: We evaluated the clinical ability of pattern electroretinogram (PERG) to detect functional losses in the affected hemifield of open-angle glaucoma patients with localized perimetric defects. METHODS: Hemifield (horizontally-defined) steady-state PERGs (h-PERGs) were recorded in response to 1.7 c/deg alternating gratings from 32 eyes of 29 glaucomatous patients with a perimetric, focal one-hemifield defect, 10 eyes of 10 glaucomatous patients with a diffuse perimetric defect, and 18 eyes of 18 age-matched normal subjects. Standard automated perimetry (SAP) and spectral-domain optical coherence tomography (SD-OCT) for retinal nerve fiber layer (RNFL) thickness also were performed. h-PERG amplitudes and ratios, calculated corresponding hemifield perimetric deviations, as well as hemiretina RNFL thicknesses were analyzed. RESULTS: h-PERG amplitudes, perimetric deviations, and RNFL thicknesses showed losses (P < 0.001) when comparing affected with unaffected hemifields of localized glaucomatous eyes. No differences were found in h-PERG amplitudes between hemifields of normal or diffuse glaucomatous eyes. h-PERG amplitude ratios (affected/unaffected hemifield) in localized glaucoma were lower (P < 0.001) than the ratios from normal or diffuse glaucomatous eyes. The areas under the receiver operating characteristic curves for h-PERG amplitude ratios, comparing localized-defect glaucomatous eyes with normal or diffuse glaucomatous eyes, were 0.93 and 0.91, respectively. CONCLUSIONS: h-PERG assessment showed good diagnostic accuracy to confirm localized glaucomatous defects detected perimetrically. This test may be particularly useful in cognitively impaired patients or young/nonverbal patients unable to provide reliable visual fields. TRANSLATIONAL RELEVANCE: h-PERG provides a sensitive objective measure to confirm focal losses detected with SAP and/or RNFL thickness analysis.

Potential Effect of Cyclophosphamide on Bleb Survival in Five Patients with Multiple Sclerosis Who Underwent Glaucoma Surgery.

INTRODUCTION: The purpose of this case series was to report the potential role of cyclophosphamide (CY) on bleb survival and to evaluate the safety of the trabeculectomy procedure under immunosuppressant systemic therapy. CASE SERIES: Five eyes of five patients with unresponsive to intraocular pressure (IOP) lowering medication, progressive glaucoma, underwent mytomicin C (MMC) augmented phaco-trabeculectomy, performed by the same surgeon, A.G., during the period from May 2015 to January 2016. All patients were treated with low doses of systemic CY at the time of surgery, to control their relapsing progressive multiple sclerosis (MS) form. RESULTS: During a mean follow-up period of 20.6 ± 8.1 months, for cases of "complete success" (when the IOP was < 15 mmHg without glaucoma therapy) were observed, while one case was classified as a "qualified success" since the IOP was ≤ 15 mmHg with ß-blocker drops. There were no bleb infections, nor bleb-related complications. CONCLUSION: This study reports the safety of performing the filtration surgical procedure under immunosuppressant systemic therapy and provides a possible explication of CY anti-fibrotic mechanism and its possible role on bleb survival. Our findings may suggest new perspectives of study in this field.

Combined deep sclerectomy and descemet stripping automated endothelial keratoplasty.

PURPOSE: The aim of this study was to evaluate a novel surgical combination of Descemet stripping automated endothelial keratoplasty (DSAEK) and deep sclerectomy (DS) for the management of concomitant corneal endothelial decompensation and uncontrolled glaucoma. METHODS: This retrospective case series noncomparative study included 9 eyes of 6 consecutive patients with coexistence of corneal edema resulting from Fuchs dystrophy or pseudoexfoliation keratopathy and medically uncompensated glaucoma; these patients underwent combined DSAEK and DS with mitomycin C and an absorbable collagen implant. Corneal graft clarity, endothelial cell density, visual acuity, intraocular pressure (IOP), and identification of complications were assessed over a 2-year follow-up. RESULTS: All eyes obtained graft clarity throughout the follow-up, with a final average endothelial cell decrease of -36% from baseline, and showed improved vision and good IOP control without hypotensive therapy. Measured at 3 and 24 months postoperation, the mean visual acuity improvement was 154% and 372% and IOP decrease was 51.1% and 46.4%, respectively. Two anterior segment complications occurred in 2 (22%) patients' eyes. This consisted of a graft dislocation and a modest IOP elevation, treated successfully. CONCLUSIONS: Combined DSAEK and DS was longitudinally associated with good corneal graft survival and IOP control, with few complications. These findings suggest that this surgical approach is a viable option for patients with coexisting glaucoma and corneal endothelial dysfunction. Our study should stimulate a multicenter, randomized, controlled trial of our technique.

Subfoveal choroidal blood flow and central retinal function in early glaucoma.

PURPOSE: To assess subfoveal choroidal blood flow (ChBF) in patients with early manifest glaucoma (EMG) and to compare blood flow with functional measures of central retinal integrity, standard automated perimetry (SAP) and pattern electroretinogram (PERG). METHODS: Subfoveal ChBF was determined by confocal, real-time laser Doppler flowmetry in 24 patients with EMG [>-6 dB mean deviation (MD), age range: 29-77 years, visual acuity: 20/25-20/20] and 23 age-matched control subjects. All patients had a therapeutically (topical beta-blockers with or without prostaglandin analogues) controlled intraocular pressure (IOP < 20 mmHg). Subfoveal choroidal blood volume (ChBVol), velocity (ChBVel) and ChBF were determined as the average of three 60 second recordings. In all patients and controls, the PERG and SAP (Humphrey 30-2), following standardized protocols, were also recorded. RESULTS: In patients with EMG, reductions in average ChBVel and ChBF were roughly equal, respectively, by 30% and 33.4% (p < 0.01), when compared to control subjects, so that there was no significant difference in ChBVol between the two groups. Pattern electroretinogram amplitudes were reduced by 46% (p < 0.01) in patients compared to controls. No correlation was found between any of the ChBF parameters and PERG amplitude, or Humphrey 30-2 MD and pattern standard deviation. CONCLUSION: The results suggest a significant alteration of both ChBVel and ChBF in EMG, which does not appear to be associated with the severity of central retinal dysfunction. These findings may contribute to a better understanding of the pathophysiology of early glaucomatous damage in EMG and have implications for the treatment of this pathologic condition.

Effect of epigallocatechin-gallate on inner retinal function in ocular hypertension and glaucoma: a short-term study by pattern electroretinogram.

BACKGROUND: Epigallocatechin-gallate (EGCG) is a powerful antioxidant with suggested neuroprotective action. The aim of this study was to evaluate the effect of short-term supplementation of EGCG on inner retinal function in ocular hypertension (OHT) and open-angle glaucoma (OAG). METHODS: Eighteen OHT and 18 OAG patients (perimetric mean deviation: >-10 dB) were randomly assigned to assume oral placebo or EGCG over a 3-month period in a randomized, placebo-controlled, double-blind, cross-over design clinical trial (clinicaltrials.gov identifier: NCT00476138). Pattern-evoked electroretinograms (PERGs) to 1.6 cycles/degree square-wave gratings, counterphased at 16 reversals/second, and standard automated perimetry (Humphrey 30-2) were assessed at the study entry (baseline), and after 3 months of placebo or EGCG. RESULTS: After EGCG, PERGs of OAG, but not OHT patients were increased in amplitude, compared either to baseline values (mean amplitude change: 0.06 log microV, p < 0.05) or to PERG amplitude values found in the same patients after placebo administration (mean change: -0.02 log microV, p not significant; difference between EGCG and placebo: 0.08 log microV, p < 0.05). In both OHT and OAG patients, standard automated perimetry did not show significant changes after either EGCG or placebo. In individual OAG patients, the magnitude of PERG amplitude increment after EGCG was inversely related (r = -0.8, p < 0.01) to corresponding baseline amplitudes. CONCLUSIONS: Although this study cannot provide evidence for long-term benefit of EGCG supplementation in OAG, and the observed effect is small, the results suggest that EGCG might favourably influence inner retinal function in eyes with early to moderately advanced glaucomatous damage.

Morpho-functional follow-up of the optic nerve in treated ocular hypertension: disc morphometry and steady-state pattern electroretinogram.

PURPOSE: To examine longitudinally optic disc structure and inner retinal function in treated ocular hypertension (OHT). MATERIALS AND METHODS: A morphometric (Heidelberg Retina Tomograph, HRT) and functional (steady-state pattern electroretinogram, PERG) evaluation of 27 OHT patients treated with topical beta-blockers and/or prostaglandin analogues and prospectively followed over a 24 +/- 6 month period. RESULTS: Compared with baseline, mean final PERG amplitude tended to increase (p < 0.01), while HRT was stable. Individual PERG amplitude increase was large (>or= 100%) in some patients (5/27), and unexplained by clinical parameters at baseline. CONCLUSIONS: In treated OHT, functional responses may improve while disc structure remains stable. The findings suggest that OHT-associated inner retinal dysfunction is at least in part reversible with therapeutic intraocular pressure control.

Structure-function relationship in ocular hypertension and glaucoma: interindividual and interocular analysis by OCT and pattern ERG.

BACKGROUND: Pattern electroretinogram (PERG) and optical coherence tomography (OCT) represent objective probes to investigate respectively the function of retinal ganglion cells and their structure as retinal nerve fiber layer (RNFL) thickness. We examined interindividual (II) correlations of PERG amplitude and RNFL thickness, as well as correlations between interocular (IO) differences in both measures, in ocular hypertension (OHT) and early glaucoma (EG) patients. METHODS: Thirty-one OHT, 34 EG (mean deviation: -1 to -6 dB) and 16 age-matched controls were examined in both eyes. Participants had clear optical media, no or moderate refractive errors and no concomitant ocular or systemic diseases. PERGs were elicited by counterphased (16.28 reversals/second) gratings (1.6 cycles/degree spatial frequency). The Fourier isolated 2nd harmonic PERG amplitude and phase were measured. RNFL thickness was quantified by means of OCT Stratus according to a standard protocol. Average, superior and inferior RNFL thicknesses were considered. RESULTS: Mean PERG amplitude was decreased (p < 0.01) in both OHT and EG patients compared to controls. Mean RNFL thicknesses were reduced (p < 0.01) in EG patients compared to both OHT and controls. In OHT patients, PERG amplitude did not correlate significantly with RNFL thickness in both II and IO analysis. In EG patients, PERG amplitude was positively correlated with RNFL thickness in both II (p < 0.005) and IO (p < 0.001) analysis. The slope of the correlation predicted that PERG losses exceeded systematically RNFL losses when the latter were between 0 and -0.25 log units. CONCLUSIONS: Both II and IO analyses revealed a lack of structure-function relationship in OHT, suggesting that, at this disease stage, PERG losses appear to affect primarily retinal/optic nerve head function. In EG they reflect both dysfunction and RNFL loss.

Posterior pole retinal thickness in ocular hypertension and glaucoma: early changes detected by hemispheric asymmetries.

PURPOSE: To evaluate retinal thickness at the posterior pole of the fundus in ocular hypertension (OHT) and open-angle glaucoma (OAG), and to correlate morphometric findings with visual sensitivity as determined by automated perimetry. METHODS: One randomly selected eye from 41 patients with clinical diagnosis of OHT (n = 25) or early to moderate OAG (n = 16) and 16 age-matched normal controls was examined. Retinal thickness was measured by Retinal Thickness Analyzer (RTA), acquiring 5 pre-defined scans covering the central 20 degrees of the fundus. RTA average thickness and thickness profile data, including hemispheric asymmetries calculated as relative (superior/inferior and nasal/temporal) or absolute (vertical and horizontal, ie, independent of which hemisphere was thinner) parameters, were calculated. For each eye, white-on-white Humphrey 30-2 visual field results were analyzed, in addition to standard global indices, by quantifying perimetric sensitivities for regions of the posterior pole corresponding to those sampled by the RTA. RESULTS: On average, central retinal thickness was reduced (P < 0.05) in OAG compared with OHT or normal control eyes. Vertical hemispheric absolute thickness asymmetry was increased (P < or = 0.01) in OAG eyes compared with the other groups. Horizontal hemispheric absolute thickness asymmetry was increased (P < 0.01) in both OHT and OAG eyes, compared with control eyes. At least one of the RTA parameters was altered in 13 of 25 OHT (52%) and 12 of 16 OAG eyes (75%), most frequently involving thickness asymmetries. In OAG, but not OHT eyes, superior/inferior asymmetry was positively (r = 0.69, P < 0.01) correlated with the corresponding asymmetry in perimetric sensitivity. CONCLUSIONS: The RTA can reveal increased hemispheric thickness asymmetries in both OHT and OAG eyes. In OAG eyes thickness asymmetries are associated with corresponding perimetric asymmetries. The findings in OHT eyes suggest that localized anatomic and functional damage to inner retina may not develop in parallel early in the disease process.

Underestimate of tonometric readings after photorefractive keratectomy increases at higher intraocular pressure levels.

PURPOSE: To determine whether tonometric readings of increases in intraocular pressure (IOP) during the water-drinking test (WDT) are affected by variations in central corneal thickness (CCT) induced by photorefractive keratectomy (PRK). METHODS: Data from 30 randomly selected eyes of 30 patients (18 men and 12 women; mean age, +/- SD: 33.9 +/- 7.6 years) undergoing bilateral PRK for myopia (-6.57 +/- 2.39 D) were obtained. Objective refraction, anterior radius of corneal curvature (R), CCT, and IOP measurements at baseline and at different time intervals after ingestion of 1 L of water within 5 minutes, were performed before and 6 months after PRK. All measured IOPs were recalculated by a correction factor for R and CCT and expressed as corrected intraocular pressure (IOPC) measurements. RESULTS: The mean R +/- SD was 7.84 +/- 0.20 and 8.76 +/- 0.34 mm, and the mean CCT was 544.83 +/- 19.69 and 453.97 +/- 29.95 microm, before and after PRK, respectively. The mean IOP at baseline was 15.05 +/- 2.78 and 9.83 +/- 2.56 mm Hg, and during WDT was 18.32 +/- 3.42 and 11.42 +/- 3.10 mm Hg at 10 minutes, 18.59 +/- 2.99 and 11.54 +/- 2.54 mm Hg at 20 minutes, 17.80 +/- 2.85 and 10.87 +/- 2.22 mm Hg at 30 minutes, 16.35 +/- 3.02 and 10.26 +/- 2.21 mm Hg at 45 minutes, and 14.90 +/- 2.52 and 9.81 +/- 2.32 mm Hg at 60 minutes, before and after PRK, respectively. The mean IOPC at baseline was 13.64 +/- 2.33 and 13.05 +/- 2.98 mm Hg, and during WDT was 16.61 +/- 2.77 and 15.08 +/- 3.59 mm Hg at 10 minutes, 16.96 +/- 2.69 and 15.33 +/- 2.96 mm Hg at 20 minutes, 16.10 +/- 2.50 and 14.42 +/- 2.60 mm Hg at 30 minutes, 14.92 +/- 2.72 and 13.62 +/- 2.65 mm Hg at 45 minutes, 13.82 +/- 2.27 and 13.05 +/- 2.55 mm Hg at 60 minutes, before and after excimer laser treatment, respectively. Pre- and postoperative IOPs and percentages of IOP increase differed significantly (P < 0.05), in particular at the peak, as did IOPCs but not the percentages of increase in IOPC, apart from the highest values. CONCLUSIONS: Corneal changes after PRK for myopia may induce an uneven underestimate of the IOP increases. The inadequacy of a correction factor to compensate for CCT and R at high IOP levels indicates that other biomechanical factors may play a role when the cornea is subjected to dynamic actual IOP variation. Such increase of the well-known underestimate of IOP after PRK at higher actual IOPs may have significant clinical implications in tonometric assessment of subjects at risk of glaucomatous damage.

Flicker-evoked response measured at the optic disc rim is reduced in ocular hypertension and early glaucoma.

PURPOSE: To determine in patients with ocular hypertension (OHT) or early glaucoma (EOAG) the change in blood flow measured at the neuroretinal rim of the optic disc in response to a 15-Hz diffuse green luminance flicker, a stimulus that activates predominantly the ganglion cell magnocellular pathway. METHODS: Thirteen patients with EOAG, 29 with OHT, and 16 age-matched control subjects, all with excellent fixation, were examined. Blood flow (F(onh)) at the neuroretinal rim of the optic disc was continuously monitored by laser Doppler flowmetry before and during exposure to a 15-Hz, 30 degrees field green luminance flicker. The response of F(onh) to this stimulus (RF(onh)) was expressed as percentage change in F(onh) between baseline and the last 20 seconds of flicker. Two to three temporal sites of the disc were tested, and the highest RF(onh) was considered for further analysis. RF(onh) results in patients were correlated with morphologic (cup-to-disc area ratio, cup shape neuroretinal rim area) and functional (perimetric mean deviation and pattern electroretinogram amplitude) clinical parameters. RESULTS: In the patients with OHT or EOAG, F(onh) and RF(onh) were both reduced compared with their respective values in the control group. Both quantities decreased significantly with neuroretinal rim area when the patients' data were pooled. No significant correlation was found between F(onh) or RF(onh) and the other morphometric and functional parameters. The group-averaged time course of RF(onh) was not significantly different from that in the normal subjects. CONCLUSIONS: Luminance flicker-evoked RF(onh) is abnormally reduced in patients with OHT or EOAG, indicating an impairment of neurally mediated vasoactivity. The data suggest that PERG-derived neural activity and flicker-evoked RF(onh) can be independently altered early in the disease process.

Tonometric changes of latanoprost-induced intraocular pressure reduction after photorefractive keratectomy.

PURPOSE: To assess whether tonometric measurements of the drop in intraocular pressure (IOP) induced by 0.005% latanoprost are modified after photorefractive keratectomy (PRK). METHODS: Data from 24 randomly selected eyes of 24 patients (12 men and 12 women, mean age +/- SD: 31.7 +/- 6.2 years) who were undergoing bilateral PRK for myopia (-6.38 +/- 2.26 D) were obtained. Objective refraction, central corneal thickness (CCT), anterior radius of corneal curvature (R), and IOP measurements at baseline and 24 hours after 1 drop of 0.005% latanoprost, were performed before and 6 months after PRK. All measured IOPs were recalculated by a correction factor for CCT and R and expressed as true IOP (IOPT) measurements. RESULTS: The mean CCT +/- SD was 544.58 +/- 36.03 and 463.21 +/- 38.59 micro m, and the anterior radius of corneal curvature was 7.73 +/- 0.26 and 8.33 +/- 0.37 mm, before and after PRK, respectively. The mean IOP at baseline was 15.8 +/- 2.92 and 12.23 +/- 2.37 mm Hg, and after latanoprost administration was 12.54 +/- 1.97 and 10.19 +/- 1.47 mm Hg, before and after PRK, respectively. The mean IOPT at baseline was 15.46 +/- 1.08 and 16.18 +/- 2.31 mm Hg, and after latanoprost administration was 11.85 +/- 1.56 and 12.96 +/- 1.71 mm Hg, before and after PRK, respectively. The mean IOP and IOPT reductions after latanoprost administration were, respectively, 3.25 +/- 1.66 and 3.61 +/- 1.7 mm Hg before PRK, and 2.03 +/- 1.42 and 3.22 +/- 1.79 mm Hg after PRK. Pre- and postoperative IOP reduction significantly differed (P < 0.001), but not IOPT. CONCLUSIONS: The effect of hypotensive drugs on IOP readings may be underestimated because of measurement errors due to CCT reduction and R increase after PRK for myopia. Misdiagnosis of reduced pharmacologic efficacy may be avoided if the measured IOP is corrected by a proper nomogram.

Ultrasound of the horizontal rectus muscle insertion sites: implications in preoperative assessment of strabismus.

PURPOSE: To determine the reproducibility and accuracy of ultrasonographic (US) measurements of distances between the corneoscleral limbus and the insertion site of the medial (MR) or lateral rectus (LR) muscle compared with intraoperative measurements in patients with strabismus. METHODS: One eye in each of 17 patients with postoperative secondary strabismus caused by over- or undercorrected eso- and exotropia and one eye of each of 19 patients with previously untreated strabismus underwent five repeated measurements by high-resolution ultrasonography of the distance from the corneoscleral limbus to the muscle insertion and three actual intraoperative measurements. Reproducibility, expressed as the coefficient of variation, accuracy (relative error) of US measurements, and the agreement with intraoperative measurements were assessed. RESULTS: The coefficients of variation for US data were 2.02% and 3.18% for the MR and 7.33% and 11.77% for the LR, in the surgical and untreated groups, respectively. The relative error was 6.15% +/- 8.14% (mean +/- SD) and 3.66% +/- 12.83% for the MR muscle, and 12.21% +/- 10.66% and -7.69% +/- 7.83% for the LR muscle, in the surgical and untreated groups, respectively. The 95% limits of agreement (mean +/- 2 SD) between the US and intraoperative measurements were 0.65 +/- 1.82 and 0.15 +/- 1.42 mm for the MR muscle, and 1.12 +/- 2.01 and -0.49 +/- 0.98 mm for the LR muscle, in the surgical and untreated groups, respectively. CONCLUSIONS: The results indicate good reliability and accuracy of US readings and suggest a potential usefulness in preoperative assessment of patients with strabismus with surgical failure and missing preoperative clinical data.