Nepafenac 0.3% after Cataract Surgery in Patients with Diabetic Retinopathy: Results of 2 Randomized Phase 3 Studies.

PURPOSE: To demonstrate the efficacy and safety of once-daily nepafenac 0.3% ophthalmic suspension versus vehicle, based on clinical outcomes, after cataract surgery in patients with diabetes. DESIGN: Two prospective, randomized, multicenter, double-masked, vehicle-controlled phase 3 studies. PARTICIPANTS: Total, 615 patients in study 1 and 605 patients in study 2. METHODS: Patients were randomized (1:1) to topical nepafenac 0.3% or vehicle once-daily starting the day before surgery and continuing for 90 days thereafter. MAIN OUTCOME MEASURES: Key efficacy variables were: patients (%) in whom macular edema (ME) developed (≥30% increase from preoperative baseline central subfield macular thickness) within 90 days after cataract surgery and the patients (%) with a best-corrected visual acuity (BCVA) improvement of ≥15 letters from preoperative baseline through day 14 maintained through day 90. Secondary end points included: patients (%) with a BCVA improvement of ≥15 letters from preoperative baseline through days 90 and 60 and safety over 3 months. RESULTS: A significantly lower percentage of patients demonstrated ME within 90 days after surgery with nepafenac 0.3% versus vehicle (study 1: 2.3% vs. 17.3%; P < 0.001; study 2: 5.9% vs. 14.3%; P = 0.001; pooled: 4.1% vs. 15.9%; P < 0.001). The percentage of patients achieving a ≥15-letter improvement from baseline through day 14 maintained through day 90 with nepafenac 0.3% versus vehicle was 61.7% versus 43.0% (P < 0.001) in study 1, 48.8% versus 50.5% (P = 0.671) in study 2, and 55.4% versus 46.7% (P = 0.003) in the pooled analysis. A greater percentage of patients treated with nepafenac 0.3% versus vehicle in study 1 and similar percentage in study 2 had a BCVA improvement of ≥15 letters from preoperative baseline through day 90 (77.2% vs. 67.7% [P = 0.009] and 65.4% vs. 65.9% [P = 0.888]) and through day 60 (76.2% vs. 64.7% [P = 0.002] and 68.9% vs. 62.1% [P = 0.092]). No unanticipated adverse events were observed. CONCLUSIONS: These studies demonstrated the clinical benefits of nepafenac 0.3% over vehicle in reducing the risk of postoperative ME, with the integrated analysis showing improved BCVA after cataract surgery in patients with diabetic retinopathy, with no unanticipated safety events.

Twice-daily brinzolamide/brimonidine fixed combination versus brinzolamide or brimonidine in open-angle glaucoma or ocular hypertension.

PURPOSE: To compare the intraocular pressure (IOP)-lowering efficacy and safety of brinzolamide 1% and brimonidine 0.2% fixed combination (BBFC) with that of brinzolamide 1% or brimonidine 0.2% monotherapy, all dosed 2 times per day (BID). DESIGN: Six-month, phase 3, randomized, multicenter, double-masked clinical trial. PARTICIPANTS: A total of 560 patients with primary open-angle glaucoma or ocular hypertension who had insufficient IOP reduction with their current therapeutic regimen or who were receiving ≥ 2 IOP-lowering medications. INTERVENTION: Patients received BBFC (n = 193), brinzolamide 1% (n = 192), or brimonidine 0.2% (n = 175) BID. MAIN OUTCOME MEASURES: The primary end point was mean change in diurnal IOP from baseline to month 3. Supportive end points included mean diurnal IOP change from baseline at week 2, week 6, and month 6; and mean IOP, mean IOP change from baseline, mean percentage IOP change from baseline, and percentage of patients with IOP <18 mmHg at week 2, week 6, month 3, and month 6 at each assessment time point (i.e., 9 am, 11 am, and 4 pm). Adverse events were recorded throughout the study. RESULTS: Baseline diurnal IOP was similar among groups (mean ± standard deviation: BBFC, 25.9 ± 0.19 mmHg; brinzolamide, 25.9 ± 0.20 mmHg; brimonidine, 26.0 ± 0.19 mmHg). At month 3, BBFC lowered mean diurnal IOP from baseline to a significantly greater extent than brinzolamide (least squares [LS] mean difference: -1.4 mmHg; P < 0.0001; t test) and brimonidine (LS mean difference: -1.5 mmHg; P < 0.0001). All supportive end points corroborated the results of the primary efficacy analysis. Mean percentage reductions in IOP from baseline were 26.7% to 36.0% with BBFC, 22.4% to 27.9% with brinzolamide, and 20.6% to 31.3% with brimonidine. The most common adverse drug reactions were ocular side effects, including hyperemia, blurred vision, allergic-type reactions, and discomfort. The incidence of hyperemia of the eye was slightly lower with brinzolamide than with BBFC and brimonidine, whereas blurred vision and ocular discomfort were slightly more common with BBFC than with brinzolamide or brimonidine. CONCLUSIONS: Brinzolamide 1% and brimonidine 0.2% fixed combination administered BID had a significantly greater IOP-lowering effect than either brinzolamide or brimonidine alone and displayed a safety profile consistent with its individual components.

[Examination of accommodation in pseudophakic eyes]. / Az akkomodáció vizsgálata pseudophakiás szemeken.

UNLABELLED: Some patient with monofocal intraocular lens can achieve good near visual acuity with distance correction after cataract surgery. Understanding and measuring this phenomenon also called pseudoaccommodation can help to develop new technology to substitute or restore accommodation in pseudophakic eyes. AIM: I. To measure accommodation after cataract surgery. II. To measure anterior chamber depth with Scheimpflug imaging and comparing results with standard, ultrasonic data. III. To compare anterior chamber depth data, repeatability, reproducibility and reliability with a new optical device, the anterior segment optical coherent tomography (Visante OCT) and immersion ultrasound method in phakic eyes. METHODS: I. We observed accommodation with defocusing technique, partial coherent interferometry method and measuring anterior chamber depth changing during ciliary muscle blocking. II. We measured anterior chamber depth with Pentacam and data were compared to standard ultrasonic method in phakic and pseudophakic eyes. III. We analyzed anterior chamber depth data, repeatability, reproducibility and reliability obtained by two observers using Visante OCT. RESULTS: I. A total accommodation amplitude of 0,83 D was observed with defocusing technique. Intraocular lens movement were negligible measured by partial coherent interferometry method using physiological accommodation stimulus. Mean movement of intraocular lens was 0.18 mm during blocking of the ciliary muscle. II. Pentacam and ultrasonic device measure the same anterior chamber depth in phakic eyes, but in pseudophakic eyes optical method measures significantly shallower anterior chamber depth. III. Anterior segment optical coherent tomography measures deeper anterior chamber depth than immersion ultrasonic device in phakic eyes. CONCLUSIONS: Accomodation and pseudoaccommodation observed in pseudophakic eyes is hard to measure and only parts of this process can be measured with each technique. Anterior chamber depth data varies by the measuring technique. Repeatability, reproducibility and reliability of anterior chamber depth data were better with optical technique.

Age-related impairment of neurovascular coupling responses: a dynamic vessel analysis (DVA)-based approach to measure decreased flicker light stimulus-induced retinal arteriolar dilation in healthy older adults.

Aging is a major risk factor for vascular cognitive impairment and dementia (VCID). Recent studies demonstrate that cerebromicrovascular dysfunction plays a causal role in the development of age-related cognitive impairment, in part via disruption of neurovascular coupling (NVC) responses. NVC (functional hyperemia) is responsible for adjusting cerebral blood flow to the increased energetic demands of activated neurons, and in preclinical animal models of aging, pharmacological restoration of NVC is associated with improved cognitive performance. To translate these findings, there is an increasing need to develop novel and sensitive tools to assess cerebromicrovascular function and NVC to assess risk for VCID and evaluate treatment efficacy. Due to shared developmental origins, anatomical features, and physiology, assessment of retinal vessel function may serve as an important surrogate outcome measure to study neurovascular dysfunction. The present study was designed to compare NVC responses in young (< 45 years of age; n = 18) and aged (> 65 years of age; n = 11) healthy human subjects by assessing flicker light-induced changes in the diameter of retinal arterioles using a dynamic vessel analyzer (DVA)-based approach. We found that NVC responses in retinal arterioles were significantly decreased in older adults as compared with younger subjects. We propose that the DVA-based approach can be used to assess NVC, as a surrogate cerebromicrovascular outcome measure, to evaluate the effects of therapeutic interventions in older individuals.

Anterior segment changes with age and during accommodation measured with partial coherence interferometry.

PURPOSE: To evaluate anterior segment alterations with age and during accommodation in different age groups. SETTING: Department of Ophthalmology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. METHODS: Fifty-three subjects (101 normal eyes) were enrolled in this study and divided into 3 age groups: younger than 30 years (Group 1), between 31 years and 44 years (Group 2), and older than 45 years (Group 3). The total amplitude of accommodation was determined with a defocusing technique, and anterior segment measurements were performed by partial coherence interferometry. RESULTS: Group 1 comprised 32 eyes; Group 2, 37 eyes; and Group 3, 32 eyes. The total amplitude of accommodation decreased with age (P<.0001). With the target position at infinity, the lens thickness (LT) and anterior segment length (ASL) increased and the anterior chamber depth (ACD) decreased significantly with age (P<.0001). During accommodation in the youngest group, the mean change in LT was 36.3 mum/diopter (D) and in ACD, -26.7 mum/D. The mean accommodation-induced ACD change was -0.08 mm +/- 0.06 (SD) in Group 1, -0.064 +/- 0.087 mm in Group 2, and -0.03 +/- 0.06 mm in Group 3 (P = .0004). The mean LT change during near fixation was 0.109 +/- 0.063 mm in Group 1, 0.103 +/- 0.136 mm in Group 2, and 0.006 +/- 0.05 mm in Group 3 (P<.0001). The mean ASL change during accommodation was 0.029 +/- 0.037 mm, 0.039 +/- 0.114 mm, and -0.023 +/- 0.051, respectively (P<.0001). CONCLUSIONS: In addition to forward movement of the anterior lens surface with age, the posterior surface moved backward. Alterations in LT and ACD sufficient for a unit of refractive power change during accommodation might be smaller than previously thought. Anterior shifting of the lens may also participate in the accommodative response.

Histological examination of primary posterior capsule plaques.

PURPOSE: To understand the source and evolution of the cellular elements of posterior capsule plaques. SETTING: Department of Ophthalmology, University of Sciences, Faculty of Medicine, Pécs, Hungary. METHODS: In 24 eyes of 24 patients, the primary fibrotic plaques were carefully peeled off the posterior capsule with forceps and sent for histological examination. The samples were stained with hematoxylin-eosin and with picrosirius to demonstrate collagen content. RESULTS: Most plaques were found in elderly patients with mature cataracts. However, one was found in a patient with congenital cataract. The histological examination revealed different stages of plaques, permitting discrimination of early (cellular), transitional, and late (fibrotic) stages. The plaques in the early stage contained cuboidal cells with nuclei; collagen deposition led to the development of the transitional stage; and further collagen deposition led to the fibrotic stage. There was no significant correlation between the maturity of the cataract and the plaque stage, but other factors such as previous eye surgery (vitrectomy, glaucoma surgery), long-standing diabetes mellitus (DM), and a high degree of myopia appeared to contribute to the development of plaques. CONCLUSIONS: Primary posterior capsule plaques were found primarily in elderly patients with mature cataracts but were also present post vitrectomy in those who had DM from a young age and had early stages of cataract. In the early plaque stage, cells with nuclei were found. It follows that plaques are capable of proliferation at this stage, aggravating visual disturbance. Therefore, removing the plaques by peeling from the posterior capsule or by posterior capsulorhexis during surgery is suggested.

Assessment and reproducibility of anterior chamber depth measurement with anterior segment optical coherence tomography compared with immersion ultrasonography.

PURPOSE: To measure anterior chamber depth (ACD) with an anterior segment optical coherence tomography (AS-OCT) and a standard ultrasonic (US) axial scan (A-scan) device using an immersion technique and to assess repeatability, reproducibility, and correlations of the measurements. SETTING: Department of Ophthalmology, Medical Health and Science Center, University of Debrecen, Debrecen, Hungary. METHODS: Sixty healthy eyes of 41 patients were enrolled in a study. The central ACD was measured 5 times with AS-OCT (Visante, Carl Zeiss Meditec) using its chamber tool and 5 times with a US A-scan device (UltraScan Imaging System, Alcon Laboratories) using an immersion method. The measurements were performed consecutively by 2 independent observers. RESULTS: The mean ACD measured with AS-OCT was 3.12 mm +/- 0.33 (SD) by observer 1 and 3.11 +/- 0.33 mm by observer 2 (P = .78). The repeatability was 0.8% +/- 0.4% and 1.9% +/- 1.4%, respectively. The reproducibility was 0.23%. The reliability coefficient with AS-OCT was 99.6%. The mean ACD measured with immersion US A-scan was 2.98 +/- 0.33 mm by observer 1 and 2.95 +/- 0.34 mm by observer 2 (P = .68) . The repeatability was 6.4% +/- 3.8% by observer 1 and 8.5% +/- 4.9% by observer 2. The reproducibility was 0.88%. The reliability coefficient was 87.1% for US A-scan measurements. The difference between ACD values with AS-OCT and values with US A-scan was statistically significant (P = .02). The correlation (r) between AS-OCT and US A-scan was 0.732 (P<.0001) by observer 1 and 0.802 (P<.0001) by observer 2. CONCLUSIONS: Anterior chamber measurements were significantly deeper with AS-OCT than with US immersion A-scan. Repeatability of ACD measurements was better with AS-OCT than with immersion US, and reproducibility was equal with the 2 methods.

Scheimpflug image-based changes in anterior segment parameters during accommodation induced by short-term reading.

PURPOSE: To analyze the effect of the accommodation on the anterior segment data (corneal and anterior chamber parameters) induced by short-time reading in a healthy, nonpresbyopic adult patient group. METHODS: Images of both eyes of nonpresbyopic volunteers were captured with a Scheimpflug device (Pentacam HR) in a nonaccommodative state. Fifteen minutes of reading followed and through fixation of the built-in target of Pentacam HR further accommodation was achieved and new images were captured by the device. Anterior segment parameters were observed and the differences were analyzed. RESULTS: Fifty-two healthy eyes of 26 subjects (range 20.04-28.58 years) were analyzed. No significant differences were observed in the keratometric values before and after the accommodative task (p = 0.35). A statistically significant difference was measured in the 5.0-mm-diameter and the 7.0-mm-diameter corneal volume (p = 0.01 and p = 0.03) between accommodation states. Corneal aberrometric data did not change significantly during short-term accommodation. Significant differences were observed between nonaccommodative and accommodative states of the eyes for all measured anterior chamber parameters. CONCLUSIONS: Among the parameters of the cornea, only corneal volume changed during the short-term accommodation process, showing some fine changes with accommodation of the cornea in young, emmetropic patients. The position of the pupil and the anterior chamber parameters were observed to change with accommodation as captured by a Scheimpflug device.

Pseudophakic accommodation and pseudoaccommodation under physiological conditions measured with partial coherence interferometry.

PURPOSE: To distinguish pseudophakic accommodation from pseudoaccommodation by measuring the physiologically and pharmacologically induced anterior chamber depth (ACD) shifts. SETTING: Department of Ophthalmology, University of Debrecen, Debrecen, Hungary. METHODS: This study comprised 100 pseudophakic eyes of 79 patients. Forty patients (Group 1) received the AcrySof MA60AC intraocular lens (IOL) (Alcon Laboratories), 50 patients (Group 2) received the SA60AT IOL (Alcon Laboratories), and 10 patients (Group 3) received the apodized diffractive SA60D3 ReSTOR IOL. Visual function was evaluated a mean of 10.2 months +/- 9.2 (SD) postoperatively, and the total pseudoaccommodative amplitude was determined with a defocusing technique. To distinguish pseudophakic accommodation from pseudoaccommodation, ACD measurements were performed using partial coherence interferometry during distance fixation and physiologic accommodation after pharmacologic relaxation of the ciliary muscle. RESULTS: Best corrected distance and near visual acuities were similar in the 3 groups (P = .75 and P = .08, respectively). Distance corrected near visual acuity was significantly better in Group 3 (P < .001), with all eyes achieving J1 or better. Three percent in Group 1 and 8% in Group 2 achieved J1 or better. Subjective accommodation was similar in Groups 1 and 2 (-0.82 +/- 0.18 diopter [D] and -1.00 +/- 0.35 D, respectively; P = .3). Group 3 had an accommodation curve with 2 peaks. Intraocular lens movement differences between the groups were not significant (physiologic stimulus: P = .07; cyclopentolate: P = .46), and significant ACD shifts from baseline were not detected (physiologic stimulus: P = .14; cyclopentolate: P = .10). CONCLUSIONS: Pseudoaccommodative amplitude of the investigated monofocal IOLs was independent of IOL movement. Anterior shift did not affect good near visual acuity with the AcrySof ReSTOR IOL.

Comparison of central corneal thickness measurements with a new optical device and a standard ultrasonic pachymeter.

PURPOSE: To compare central corneal thickness (CCT) values obtained with ultrasonic pachymetry and a new optical method using partial coherence interferometry (PCI). SETTING: Department of Ophthalmology, Medical Health and Science Center, University of Debrecen, Debrecen, Hungary. METHODS: The study comprised 136 eyes of 70 patients whose spherical refractive error was not greater than +/-6.0 diopters (D) and whose keratometric astigmatism was not greater than 2.0 D. Central corneal thickness was measured 5 times with a new optical device (ACMaster, Zeiss) and with an ultrasonic pachymeter (AL-2000, Tomey). All measurements were obtained by the same investigator. RESULTS: Mean CCT was 531.2 microm +/- 3.9 (SD) with PCI and 547.8 +/- 36.0 microm with the ultrasonic device. The difference between groups was significant (P = .001). There was no difference between CCT values measured in right and left eyes (P = .55) with ultrasonography and PCI (P = .67). The coefficient variation was 0.73% for PCI and 6.5% for ultrasonography. Correlation between the CCT measurements with both devices was strong and statistically significant (Spearman correlation = .91, P = .001). CONCLUSIONS: Mean CCT values measured by the PCI method were significantly smaller than those measured by the ultrasonic device. Central corneal thickness measured with PCI is more reproducible and seems to be more reliable than that measured by ultrasonography.

Once-daily nepafenac ophthalmic suspension 0.3% to prevent and treat ocular inflammation and pain after cataract surgery: phase 3 study.

PURPOSE: To evaluate once-daily nepafenac 0.3% to prevent and treat ocular pain and inflammation after cataract surgery. SETTING: Sixty-five centers in the United States and Europe. DESIGN: Randomized double-masked vehicle- and active-controlled phase 3 study. METHODS: Patients received nepafenac 0.3% once daily, nepafenac 0.1% 3 times daily, or their respective vehicles from day -1 to day 14 after cataract extraction. An additional drop of study drug was administered 30 to 120 minutes preoperatively. The primary endpoint was the percentage of patients with a cure for inflammation (score of 0 for both aqueous cells and flare) at day 14. RESULTS: Of randomized patients, 817 received nepafenac 0.3%, 819 received nepafenac 0.1%, and 200 and 206 received the respective vehicles. Significantly more nepafenac 0.3% patients had no inflammation (68.4% versus 34.0%) and were pain free (91.0% versus 49.7%) at day 14 than vehicle patients (both P<.0001). Nepafenac 0.3% was noninferior to nepafenac 0.1% for inflammation (95% confidence interval [CI], -5.73% to 3.17%) and pain-free rates (95% CI, -3.08% to 2.70%). At all postoperative visits, fewer treatment failures (P≤.0012) and more clinical successes (P ≤ .0264) were observed with nepafenac 0.3% versus vehicle. Nepafenac 0.3% was well tolerated and had a safety profile comparable to that of nepafenac 0.1%. CONCLUSIONS: Once-daily nepafenac 0.3% was noninferior to nepafenac 0.1% 3 times daily for prevention and treatment of ocular inflammation and pain following cataract surgery. The safety of nepafenac 0.3% was comparable to that of nepafenac 0.1%, with the added convenience of once-daily dosing. FINANCIAL DISCLOSURE: Drs. Modi, Lehmann, Walters, Fong, Christie, Roel, Nethery, and Reiser have been paid consultants to Alcon Research, Ltd. Ms. Sager is an employee of Alcon Research, Ltd. Drs. Tsorbatzoglou, Philipson, and Traverso have no financial or proprietary interest in any material or method mentioned.