Efficacy of the fixed combinations of bimatoprost or latanoprost plus timolol in patients uncontrolled with prostaglandin monotherapy: a multicenter, randomized, investigator-masked, clinical study.

PURPOSE: To compare the efficacy and tolerability of a once-daily evening dose of bimatoprost/timolol fixed combination (BTFC) with that of a once-daily evening dose of latanoprost/timolol fixed combination (LTFC) in patients not controlled with prostaglandins analogues monotherapy. METHODS: A total of 82 patients on prostaglandin analogues monotherapy were enrolled in this prospective, multicenter, investigator masked, clinical study and were randomized to either BTFC (n=47) or LTFC (n=35) topical therapy once at night for 12 weeks. The primary endpoint of the study was to compare the mean daily intraocular pressure (IOP) reduction from baseline between the two treatment arms. Secondary endpoints included the mean daily IOP at 1 and 3 months compared to baseline and the percentage of patients showing a mean IOP reduction from baseline greater than or equal to 15% or 20%. RESULTS: Mean IOP at baseline was 22.7+/-2.0 and 22.1+/-2.6 mmHg in the BTFC and LTFC groups, respectively (p=0.23). Both treatments were effective in reducing the IOP from baseline. The mean IOP reduction was significantly greater in the BTFC group than in the LTFC group (-21.4% vs -13.7%, p<0.001). A higher percentage of patients in the BTFC group showed a mean IOP reduction from baseline >or=15% (72.3% vs 40.0%) and >or=20% (61.7% vs 17.1%) compared to patients in the LTFC group. CONCLUSIONS: Both BTFC and LTFC were more effective versus the monotherapy with prostaglandin analogues. BTFC demonstrated higher performance than LTFC in terms of relative IOP reduction.

The influence of posterior capsule opacification on scanning laser polarimetry.

PURPOSE: To evaluate the influence of posterior capsule opacification (PCO) on GDx parameters in a population of pseudophakic, non-glaucomatous patients who underwent Nd:YAG laser capsulotomy (YLC). METHODS: The posterior capsules were photographed with a Topcon digital camera and each image was then entered into the EPCO 2000 software and evaluated independently by three examiners. The EPCO 2000 software was used to calculate the fibrosis index (FI) and the pearl index (PI) for the central 1.5, 2.5, and 3.5 mm of the posterior capsule. Scanning laser polarimetry was performed with GDx before and after YLC. We compared the GDx readings obtained before and after the YLC using paired Student's t-test. The parameters that varied significantly after YLC were subsequently used for regression analysis. Stepwise multiple linear regression was used to analyse the impact of the change in the amount of FI and PI on change in GDx parameters after YLC. RESULTS: In total, 158 patients were enrolled (74 men, 84 women). The mean age was 69.46+/-8.83 years (range 46-83 years). The interobserver agreement among the three experts was found to be good (repeatability coefficient R=1.51, 1.49, 1.49 for observer A vs B, A vs C, and B vs C respectively). One-sample Student's t-test show no difference between all GDx parameters before and after YLC except for Symmetry, Superior/Nasal ratio, Inferior Ratio, and Temporal-Superior-Nasal-Inferior-Temporal (TSNIT). Stepwise multiple regression showed that the two variables of greatest significance for changes in Symmetry were the FI in the central 1.5 and the PI in the central 3.5 mm (P=0.02). Superior/nasal ratio was shown to be most strongly correlated to the FI in the central 1.5 mm and PI in the central 3.5 mm (P<0.001), whereas the variable of greatest significance to Inferior Ratio was PI in the central 3.5 mm (P=0.03). Finally, TSNIT was most strongly correlated to FI in the central 1.5 mm and FI in the central 2.5 mm (P<0.001). CONCLUSION: Presence of capsular fibrosis seems to be more clinically relevant in the central zone, whereas pearls tend to be clinically significant in the central 3.5 mm area. Hence, it might be worthwhile assessing the amount of PCO in pseudophakic patients when performing scanning laser polarimetry. Investigators should ensure that the type of PCO and the size of the area analysed are documented in the notes in order to interpret GDx findings appropriately.

Efficacy and safety of bimatoprost in patients with uncontrolled glaucoma as alternative to filtration surgery.

PURPOSE: To evaluate the efficacy and safety of bimatoprost 0.03% as an alternative to filtration surgery in patients with uncontrolled glaucoma. DESIGN: Interventional study. METHODS: A total of 83 consecutive patients (83 eyes) awaiting glaucoma surgery were enrolled in eight ophthalmic centers. Reasons for listing were inadequate intraocular pressure (IOP) control despite medical therapy and documented progression of visual field loss. All patients discontinued the previous treatment and were switched to bimatoprost 0.03% QD (one drop at 9 pm). The primary efficacy outcome was a 20% IOP reduction from baseline at each timepoint. IOP was measured at day 7, day 30, day 60, and day 90 of treatment; less than 20% IOP reduction was considered as a failure. RESULTS: An IOP reduction of at least 20% was achieved in 74 patients (89.1%) after 7 days and in 64 patients (86.5%) after 30 days. Sixty-two patients (74.6%) maintained IOP readings 20% lower than baseline after 60 and 90 days. In these patients, visual field indices improved in 8 eyes (13%), and remained unchanged in 54 eyes (87%). Ocular side effects were conjunctival injection (15.6%), burning sensation (9.6%), foreign body sensation (4.8%), and eyelash growth (2.4%). CONCLUSIONS: This preliminary study shows that bimatoprost 0.03% could represent a useful therapeutic tool that might defer filtration surgery.

Effect of cataract surgery and foldable intraocular lens implantation on retinal nerve fiber layer as measured by scanning laser polarimetry with variable corneal compensator.

PURPOSE: Scanning laser polarimetry (SLP) enables the measurement of retinal nerve fiber layer (RNFL) thickness in vivo. As SLP measurements can be influenced by several conditions such as corneal birefringence, the new version GDx Access is implemented by the variable corneal compensator (VCC). The aim of this study was to evaluate the influence of cataract extraction and foldable intraocular lens (IOL) implantation on SLP parameters measured by GDx Access. METHODS: Sixty-eight eyes of 68 patients undergoing phacoemulsification with foldable IOL implantation (silicone and acrylic) were examined by SLP before and after surgery. SLP was performed using GDx Access (with VCC). Mean values for SLP parameters were compared before and after 30 days from surgery with paired two-tailed Student's t-test. RESULTS: No statistically significant differences were found between SLP parameters before and after cataract surgery, and regardless of the type of IOL implanted. CONCLUSIONS: Phacoemulsification and foldable IOL implantation do not influence RNFL parameters, as measured by GDx Access.

Acute and chronic effects of brimonidine 0.2% on intraocular pressure and pulsatile ocular blood flow in patients with primary open-angle glaucoma: an open-label, uncontrolled, prospective study.

BACKGROUND: Brimonidine has been reported to decrease aqueous production and increase uveoscleral outflow; however, the hemodynamic effects of brimonidine are still under investigation. OBJECTIVE: The purpose of this study was to report the acute and chronic effects of brimonidine 0.2% on intraocular pressure (IOP) and pulsatile ocular blood flow (pOBF) in patients with primary open-angle glaucoma (POAG). METHODS: Nonsmoking patients aged 45 to 67 years with POAG and normal blood pressure, heart rate, body mass index, and hemorheologic parameters were enrolled in the study. Brimonidine 0.2% was self-administered twice daily for 180 days. IOP and pOBF were determined using Goldmann applanation tonometry and the Langham system. All measurements were taken at baseline and 4, 8, and 12 hours after treatment and were repeated on days 7, 15, 30, 60, 90, 120, 150, and 180 of treatment. RESULTS: Of the 18 eligible patients, 10 (6 men and 4 women) were enrolled (mean age, 51.5 +/- 4.39; range, 47-64 years). When measured 12 hours after instillation, mean IOP was significantly reduced by 21.5% (P < 0.001) compared with the baseline value. The greatest decrease in IOP (-23.5%) was observed at 8 hours. After 12 hours, a significant increase (P < 0.001) in pOBF was measured. A stable IOP reduction (P < 0.001 vs baseline), as well as an increase in pOBF (P = 0.015), was recorded at the subsequent time points. The pOBF increases ranged from 22.5% at day 30 to 9.2% at day 180 of treatment. No evidence of adverse events was found at any time point. CONCLUSIONS: In this sample of patients with open-angle glaucoma, brimonidine induced a rapid reduction in IOP that was significant even after 6 months. Moreover, an increase in pOBF was observed from the first day of treatment, and remained consistent throughout the study.

Corneal temperature changes during photorefractive keratectomy using the Laserscan 2000 flying spot laser.

PURPOSE: To evaluate the thermal variations during photorefractive keratectomy (PRK) induced by a Laserscan 2000 flying spot excimer laser. METHODS: Thermal changes during PRK were recorded using a non-contact infrared thermometer on 58 eyes with an attempted correction ranging from -1.25 to -9.00 D. The eyes were randomly divided into two groups to test the thermal effects of two different ablation scan techniques: sequential and randomized modes. Thermal measurements were also performed during myopic ablations on polymethylmethacrylate (PMMA) test plates. RESULTS: On PMMA plates, a significant relationship between the amount of attempted myopic correction and thermal changes was established (P=.017 in sequential mode and P=.007 in randomized mode); this was not established for human eyes. With the sequential mode, an unexpected cooling effect after PRK was reported for each myopia subgroup (P=.003 in the low and high myopia subgroups, P<.001 in the medium myopia subgroup). With the randomized mode, the cooling effect was detected only for low amounts of myopia. CONCLUSION: Despite a high repetition rate, the Laserscan 2000 flying spot laser minimized thermal shock. In comparison with randomized (nonsequential) pulse application, sequential pulsing showed no increase in the thermal loading of corneas. In fact, a cooling effect during PRK was produced.

A randomised, double masked, clinical trial of high dose vitamin A and vitamin E supplementation after photorefractive keratectomy.

AIM: To evaluate the effect of a high dose vitamin A and E supplementation on corneal re-epithelialisation time, visual acuity and haze following photorefractive keratectomy (PRK). METHODS: Two groups of 20 patients who underwent myopic PRK were supplemented with either 25 000 IU retinol palmitate and 230 mg alpha tocopheryl nicotinate or a placebo. Clinical outcomes were evaluated up to 360 days. RESULTS: In the vitamin treated group, re-epithelialisation time was significantly faster (p = 0.029) and haze incidence was reduced (p = 0.035), especially for high myopic corrections (p = 0.043). This group also reported a significantly better uncorrected visual acuity (p = 0.043). CONCLUSIONS: High dose vitamin A and E oral supplementation may accelerate re-epithelialisation time and may reduce corneal haze formation after PRK.

The effect of early steroid treatment after PRK on clinical and refractive outcomes.

PURPOSE: To evaluate the effects of steroid treatment administered in the first days after excimer laser keratectomy (PRK) on re-epithelialization time, postoperative pain, haze and refractive outcome. METHODS: A randomised, double masked trial was carried out on two groups of patients (40 patients each), who underwent PRK. Group A (steroid group) received 0.1% fluorometholone acetate whereas group B (NSAID group) received 0.5% ketorolac tromethamine until re-epithelialization was completed. Subsequently, all 80 patients received the same steroid treatment: 0.1%, fluorometholone acetate for myopic corrections up to -5 D, or dexamethasone for myopic corrections exceeding -5 D. Both drugs were tapered off over approximately 3 months. Follow-up examinations were planned at 1, 3, 6, 12 months after surgery. RESULTS: Re-epithelialization was completed after three days, without any significant difference between groups. A higher hyperopic shift was shown in the steroid group and a more severe regression was reported in the NSAID group (p<0.001). Haze was significantly reduced in the steroid group (p=0.005), especially for myopic corrections over -5 D (p=0.015). Pain was significantly reduced in the NSAID group (p=0.002). CONCLUSION: Steroid eyedrops administered in the first days after PRK did not affect re-epithelialization time. Moreover, a modulation of the inflammatory response in this period appears to reduce haze and myopic regression in high myopic patients.

A randomized, comparative open-label study on the efficacy of latanoprost and timolol in steroid induced ocular hypertension after photorefractive keratectomy.

PURPOSE: To evaluate the effect of 0.005% latanoprost and 0.50% timolol for the treatment of steroid-induced ocular hypertension (SIOH) after excimer laser photorefractive keratectomy (PRK). METHODS: In this comparative, open-label study we enrolled 29 patients who received steroid therapy after PRK and developed intraocular pressure (IOP) elevation within 30 days of treatment. Fifteen were randomized to 0.005% latanoprost (group A) and 14 to 0.50% timolol (group B). IOP measurements were scheduled at 1, 3, 7, 15, 30, 60, 90 and 120 days of therapy. RESULTS; We did not find any real differences between latanoprost and timolol except at the 7-day and 15-day timepoints, when latanoprost reduced IOP significantly more than timolol (p=0.033, 0.035, respectively). After 7 days of therapy two of the 14 timolol-treated patients had high IOP (24 and 26 mmHg) but these promptly returned to normal when latanoprost was added. No significant differences were observed in the ocular side effects considered. CONCLUSIONS: 0.005% latanoprost is as safe and effective as 0.50% timolol in the treatment of SIOH after PRK. Both drugs provide a significant and stable IOP reduction in the majority of patients after short-term treatment. These findings are encouraging for the use of latanoprost in the management of SIOH after PRK, although further trials are necessary to consider it as a primary treatment.

Anterior chamber depth measured by two methods in myopic and hyperopic phakic IOL implant.

AIM: To evaluate the accuracy and reliability of the optical versus ultrasonic measurement of anterior chamber depth (ACD) in a group of patients affected by high myopia or hyperopia, before phakic IOL implant. METHODS: 18 consecutive patients (34 eyes) were enrolled in this study, and asked to undergo phakic IOL implant to correct high myopia or hyperopia. The mean age was 29.5 (SD 3.4) years, the male/female ratio was 10/8. 13 patients (24 eyes) were myopic (mean myopia -16.17 (4.39) D, range -9 to -24 D), whereas five patients (10 eyes) were hyperopic (mean hyperopia 7.4 (2.01) D, range 5.5-11 D). For each patient, ACD was evaluated comparing an optical system (Orbscan topograph system) with a standard A-scan ultrasound system. To evaluate the reliability of the two methods, the average of three optical and 10 ultrasonic consecutive measurements were considered. Statistical analysis was performed by means linear regression. RESULTS: The average difference between optical and ultrasound values was 0.17 (0.1) mm (4.68% (2.52%)). There was a constant underestimation of the ACD with the optical system compared with the ultrasound measurement, more evident in the hyperopic eyes (5.20% (1. 95%)) than in myopic ones (4.46% (2.72%)). The reliability of measurements, as showed by the standard deviation values, was higher in the optical system (0.03 (0.02)) than in the ultrasound (0.1 (0. 05)), with a statistical difference (p<0.001). The linear regression analysis between optical and ultrasound measurements was 0.8992 (p<0. 0001). CONCLUSIONS: The optical measurement of ACD is an accurate and reliable technique in high myopic and hyperopic eyes. It gives a small underestimation of the ACD values, but it could be preferable to the ultrasound technique, because it demonstrates more repeatability and has the advantages of a non-contact technique.

Prospective randomized comparison of simultaneous and sequential bilateral photorefractive keratectomy for the correction of myopia.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy and safety of simultaneous bilateral photorefractive keratectomy (PRK). PATIENTS AND METHODS: There were 52 patients (104 eyes) with myopia less than -6 diopters entered in this prospective trial and randomized to simultaneous or sequential bilateral PRK. Main outcome measures were uncorrected visual acuity (UCVA), percentage of eyes within +/-0.5 D of attempted outcome, present pain intensity (PPI) and total pain rating index (PRI(R)T) scores resulting from McGill the Pain Questionnaire, subjective symptoms, haze, and patient satisfaction. Follow-up extended to 14 months. RESULTS: There was no significant difference in UCVA (P=0.996) and percentage of eyes within +/-0.5 D of attempted correction (P=0.932). Present pain intensity and PRI(R)T scores were significantly higher in the sequential group (P=0.037; P=0.034). The percentage of satisfied patients after bilateral PRK was significantly higher in the simultaneous group (P=0.036). CONCLUSIONS: Simultaneous bilateral PRK was safe and effective, without any significant difference from sequential treatment.

A randomized, double-masked, clinical study of the efficacy of four nonsteroidal anti-inflammatory drugs in pain control after excimer laser photorefractive keratectomy.

OBJECTIVE: This study assessed the efficacy of 4 nonsteroidal anti-inflammatory drugs (NSAIDs) after excimer laser photorefractive keratectomy (PRK). BACKGROUND: Inadequate control of pain after PRK surgery can be a severe source of distress to patients and can interfere with their willingness to undergo a second PRK procedure. METHODS: This randomized, double-masked, placebo-controlled clinical study was conducted in 125 patients. Four NSAIDs (diclofenac, flurbiprofen, ketorolac, and indomethacin) were tested against a placebo group (artificial tears). Pain levels after PRK were quantified using Present Pain Intensity (PPI) and Pain Rating Indices based on rank values (PRI[R]) scores, both of which were calculated using patient responses to a modified McGill Pain Questionnaire. The PRI(R) consisted of 4 subscales-sensory (S), affective (A), evaluative (E), and miscellaneous (M)-as well as a total score (T). RESULTS: Three hours after PRK, no differences in PPI scores were found between the ketorolac, diclofenac, and indomethacin groups, whereas placebo was significantly less effective than the NSAIDs. Patients who received flurbiprofen reported PPI scores that were significantly lower (P < 0.001) than those of patients who received diclofenac and indomethacin, but PPI scores in the flurbiprofen and the ketorolac groups did not differ significantly. Twenty-four hours after surgery, patients treated with flurbiprofen, ketorolac, and diclofenac reported the lowest PPI scores compared with those treated with indomethacin and placebo (P < 0.001). Moreover, flurbiprofen-treated patients also had the lowest PRI(R)T scores (P < 0.001). When the pain rating index was examined by subclass, a significantly lower PRI(R)S score was detected in the flurbiprofen group at 24 hours (P < 0.001). The PRI(R)A score was significantly higher in the placebo and indomethacin groups compared with the other groups (P < 0.001). At the 48- and 72-hour time points, flurbiprofen-treated patients again reported significantly lower PPI and PRI(R)T scores (P < 0.001 for both) in pair-wise comparisons with the other treatment groups. The number of patients who self-administered additional oral analgesics did not differ significantly between the groups. However, the mean number of analgesic tablets used was significantly higher in the placebo group than in any NSAID group (P < 0.001). The ketorolac group had the largest number of patients complaining of itching (P < 0.043). No other subjective symptoms were significantly different across groups. Finally, all NSAIDs, except flurbiprofen, prolonged the mean reepithelialization period slightly (P < 0.001). CONCLUSIONS: Flurbiprofen appeared to be the most effective NSAID for the treatment of pain, even at 24 hours after surgery when pain was at a maximum.

Contrast sensitivity measured by 2 methods after photorefractive keratectomy.

PURPOSE: To study contrast sensitivity in eyes that had flying-spot excimer laser photorefractive keratectomy (PRK) and to compare a subjective method (Vision Contrast Test System [VCTS] 6500) and an objective method (visual evoked potential [VEP]) of measuring contrast sensitivity. SETTING: Istituto Clinica Oculistica, Università degli Studi, Bari, Italy. METHODS: Contrast sensitivity changes over time were evaluated in 26 eyes. The baseline values were compared with measurements 3, 6, and 12 months after PRK using the VCTS 6500 and VEP. Contrast threshold and VEP amplitude were classified by myopic correction. RESULTS: Contrast threshold values changed significantly over time (P <.001). Significant differences were found between mean contrast threshold preoperatively and 12 months postoperatively (P <.001) at all spatial frequencies. A significant relationship was established between baseline and 12 month measurements at 18 cycles per degree. Mean VEP amplitude measurements also changed significantly over time (P <.001) and showed a significant relationship between baseline and 12 month measurements (P <.001). A significant relationship was also established between baseline and 12 month VEP amplitude values at 100% of grating contrast. Patients with high myopia complained significantly more at a lower contrast threshold and at lower VEP amplitude values than patients with low myopia. CONCLUSIONS: Three months after PRK, contrast threshold and VEP amplitude values were reduced. Partial recovery was established at 6 months, although patients reported permanent impairment under low-contrast conditions, especially if the myopia correction was more than 6.0 diopters.

Retinal nerve fiber layer measurements using scanning laser polarimetry after photorefractive keratectomy.

PURPOSE: To assess the effects of corneal depth changes on retinal nerve fiber layer (RNFL) postoperative measurements in myopic patients who had undergone photorefractive keratectomy (PRK). METHODS: A total of 120 myopic patients underwent PRK for myopia (range -2 to -10 diopters) and were divided into three groups according to their myopic correction: lower than 3 diopters (low myopia group), between 3 and 6 diopters (medium myopia group), over 6 diopters (high myopia group). RNFL parameters were evaluated preoperatively and 5 days, 3 months and 6 months after surgery, using a GDx NFA II scanning laser ophthalmoscope. RESULTS: Significant changes were seen in the symmetry, superior maximum, and average thickness, comparing baseline with six-month measurements (p=0.008, 0.027, 0.015 respectively). Dividing the sample according to attempted myopic correction, it was found that mean postoperative RNFL thickness was significantly lower after PRK only in the high myopia group. Mean RNFL thickness did not change with time (p=0.884). Ablation depth was correlated with a change in RNFL thickness by the sixth postoperative month for each group. These variables were significantly related only in the high myopia group (p=0.003). CONCLUSIONS: As polarised light penetrates the ablation area, morphological and functional changes might affect Gdx NFA II measurements. It must always be borne in mind that RNFL thickness can decrease either in cases of glaucoma or after PRK for high myopia, so close attention must be paid to interpreting these measurements in patients who have undergone PRK.

A randomized, comparative study of fluorometholone 0.2% and fluorometholone 0.1% acetate after photorefractive keratectomy.

PURPOSE: To compare the efficacy and tolerance of fluorometholone 0.1% acetate and fluorometholone 0.2% eyedrops in the postoperative management of photorefractive keratectomy (PRK). METHODS: A randomised single-blind comparative study was performed on two groups of 30 patients who underwent myopic PRK. The first group was given fluorometholone 0.1% acetate and the second fluorometholone 0.2%. Uncorrected and best corrected visual acuity, haze, IOP and local tolerance were evaluated. Statistical analysis was done using parametric and non-parametric tests. RESULTS: Visual acuity did not differ in the two groups; both were homogeneous as far as refractive error and haze were concerned. Three patients (10%) treated with fluorometholone 0.2% and two patients (6.6%) with fluorometholone 0.1% acetate developed ocular hypertension, but this was not statistically significant. CONCLUSIONS: Fluorometholone 0.1% acetate was effective on inflammation after PRK, with the same efficacy as fluorometholone 0.2%.

Pars plana vitrectomy in diabetic macular edema.

PURPOSE: To ascertain the association between the improvement of diabetic macular edema and increased visual acuity after pars plana vitrectomy. METHODS: From January 1994 to December 1996 we prospectively studied 18 patients (18 eyes, 7 women and 11 men, mean age 52 years, range 37-68) with type II diabetes and clinically significant macular edema. One group was composed of 9 patients presenting diffuse macular edema (DME); a second group with 9 patients presented cystoid macular edema (CME). All patients underwent pars plana vitrectomy. RESULTS: Preoperative Snellen visual acuity was 20/143 in DME and 20/441 in CME. In both groups vision increased to 20/136 and 20/205, respectively, postoperatively. For the DME this difference was statistically significant (p<0.05) at 1 month after the surgery, but vision decreased again after 10 months reaching preoperative values. CONCLUSIONS: Our results suggest that pars plana vitrectomy for diabetic macular edema may increase visual acuity in diffuse macular edema, although this increase is only short lived.

The choroidal circulation after retinal detachment surgery.

PURPOSE: to assess the effects on choroidal perfusion of scleral buckling and vitrectomy procedures for retinal detachment. METHODS: 17 patients were included in the study: 7 underwent scleral buckling and 10 vitrectomy, for rhegmatogenous retinal detachment. pOBF Langham system evaluation was performed before and after surgery (the fellow eye served as control). Statistical analysis was based on paired t-test. RESULTS: in the scleral buckling group was found a mean change (SD) of 470 (355.32) microl/min; in the vitrectomy group the mean difference (SD) was 254.2 (132.53) microl/min. In both groups a statistically significant difference with the control was found. CONCLUSIONS: our results show that both surgical procedures affect choroidal perfusion and could impair optic nerve head feeding.