Contrast Sensitivity Changes in Center Involving Diabetic Macular Edema Treated with Aflibercept.

PURPOSE: To characterize the changes in contrast sensitivity (CS) and retinal anatomy in patients with center involving diabetic macular edema (CDME) measured from baseline to post-loading doses of aflibercept. PATIENTS AND METHODS: This single center, prospective, open-label, non-controlled evaluation of five aflibercept intravitreal injections for treatment of CDME over a 16-week period. One eye in each of the forty patients will receive aflibercept every 4 weeks. Subject testing includes measurements of central retinal thickness (CRT), best corrected visual acuity (BCVA), Pelli-Robson (PR) CS, and CamBlobs (CB) CS at 20 weeks post baseline. RESULTS: A total of 40 eyes from 40 patients with CDME were analyzed. The mean age was 62.9 ±10.6 years and 55% were male. At baseline, CRT was 365 ±94.6µm with logMAR BCVA 0.25±0.20. CS PR at baseline was 1.46±0.13 logCS compared to the normal population 1.79±0.10 logCS (P=<0.01), and the CS CB was 1.55±0.16 logCS compared to 1.92±0.08 logCS in the normal population (P=<0.01). At the completion of the study, CRT was decreased to 289 ±43.7µm (P=<0.001), and the logMAR BCVA improved to 0.18±0.02 (P=<0.05). At the same point the CS PR was 1.52±0.16 and CS CB was 1.62±0.16 logCS. At the end of the study 85% of eyes obtained BCVA of 0.3 logMAR or better. There was a reduction from baseline of 82.5% to 57.5% in the number of patients that had a CS that was two standard deviations below the mean. The greatest improvement in CS was associated with those patients that had the greatest reduction in CRT. CONCLUSION: CS impairment in patients with CDME is significant. Although treatment can be associated with improvement, there still remains a group with decreased CS that could impact activities of daily living. Earlier intervention using reduction in CS as a metric may be associated with reduced residual deficit associated with treatment.

Visual Function for Driving in Diabetic Macular Edema and Retinal Vein Occlusion Post-Stabilization with Anti-Vascular Endothelial Growth Factor.

PURPOSE: What is the level of visual function in patients with diabetic macular edema (DME) and retinal vein occlusion (RVO) post-stabilization with anti-vascular endothelial growth factor? PATIENTS AND METHODS: This observational non-controlled single center study evaluated visual function in two patient populations with macular edema 25 with diabetic macular edema and 25 with retinal vein occlusion treated following standard protocol of anti-VEGF therapy post- stabilization. RESULTS: A total of 68 eyes from 50 patients were analyzed including 18 bilateral and 7 unilateral diabetic macular edema, 14 patients with central and 11 with branch retinal vein occlusion. The mean age was 69± 11 years and 64% were male. In the RVO group: LogMAR BCVA was 0.12±0.13 compared to the unaffected eye 0.04±0.05 (P=<0.01), contrast sensitivity in the treated eye was 1.69±0.21 log units compared to 1.84± 0.15 log units in the unaffected eye (p=<0.01), the ganglion cell volume was 0.88± 0.15 mm3 in the treated eye compared to 1.04± 0.1 mm3 in the unaffected eye (P=<0.01). In the diabetic macular edema group: LogMAR BCVA was 0.17±0.13, contrast sensitivity in the treated eye was 1.16±0.21 log units compared to the normal population 1.92±0.8 log units (p=<0.01), the ganglion cell volume was 0.94± 0.14 mm3 in the treated eye compared to 1.03± 0.12 mm3 in the normal population (P=<0.001). In both groups a majority of treated eyes retained visual acuity ≥+0.4 LogMAR (diabetic macular edema 95%, RVO 96%) however contrast sensitivity was more than two standard deviations below the normal population mean in a majority of treated eyes in both groups (diabetic macular edema 88% RVO 64%). CONCLUSION: Impairment in contrast sensitivity in both groups could impact activities of daily living including driving and should prompt questions about how we advise patients regarding their level of function and the potential limitations/restrictions that should be placed on such activities.

Evaluation of contrast sensitivity and other visual function outcomes in diabetic macular edema patients following treatment switch to aflibercept from ranibizumab.

PURPOSE: This study aims to investigate changes in contrast sensitivity (CS), visual acuity (VA), central retinal thickness (CRT), and vision-related quality of life in subjects with recalcitrant diabetic macular edema switched from long-term ranibizumab treatment to aflibercept. PATIENTS AND METHODS: In this prospective, investigator-masked, single-center study, 40 patients with persistent fluid, despite previous ranibizumab treatment, were switched to aflibercept with 5 consecutive monthly doses. The primary outcome was mean change from baseline to week 20 in Pelli-Robson CS. Secondary outcomes were mean change from baseline in best-corrected VA (BCVA), CRT, and National Eye Institute 25-Item Visual Function Questionnaire score. RESULTS: Fifty eyes (baseline VA >6/30) were evaluated. A median of 21.1±11.9 (range 5-55) ranibizumab injections were administered prior to initiation of aflibercept. Mean CS improved from 1.40±0.14 log units at baseline to 1.46±0.15 log units at week 20 (P<0.001). VA improved with mean logarithm of the minimum angle of resolution BCVA of 0.33±0.19 at baseline compared with logarithm of the minimum angle of resolution BCVA of 0.28±0.16 at week 20 (P=0.0016). Mean CRT decreased from 324±85 to 289±61 µm (P<0.001). Twenty-two (55%) patients experienced an overall improvement in National Eye Institute 25-Item Visual Function Questionnaire score. Interestingly, an association was found between changes in CS and change in CRT (r2=0.385, P<0.001) and between changes in BCVA and change in CRT (r2=0.092, P=0.032). CONCLUSION: Switching from ranibizumab to aflibercept in patients with recalcitrant diabetic macular edema resulted in an improvement in all measured metrics, including CS, VA, and CRT. A majority of patients also indicated an improvement in vision-related quality of life. The finding of a stronger relationship between changes in CRT and CS compared with changes in CRT and BCVA suggests that the inclusion of CS as an endpoint may yield a more complete understanding of visual outcomes than that obtained by using VA alone.

Evaluation of contrast sensitivity and other visual function outcomes in neovascular age-related macular degeneration patients after treatment switch to aflibercept from ranibizumab.

PURPOSE: This study evaluated visual function and anatomic and vision-related quality-of-life outcomes in recalcitrant neovascular age-related macular degeneration (AMD) subjects switched to aflibercept (Eylea®) from ranibizumab (Lucentis®). METHODS: In a single-center study conducted in Barrie, ON, 40 patients with persistent fluid despite previous ranibizumab treatment were switched to aflibercept with 3 consecutive monthly doses. Main outcome measure was mean change from baseline to week 12 in Pelli-Robson contrast sensitivity (CS). Secondary outcomes were mean change in best corrected visual acuity (BCVA), central retinal thickness (CRT), and National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25) score. A two-sided paired t-test was used in the statistical data analysis to compare the means of continuous variables. RESULTS: Forty-nine eyes (baseline visual acuity [VA] >6/120) were evaluated. Ranibizumab injections (mean ± standard deviation [SD] 28.2±22.1 [range 3-86]) were administered prior to treatment switch. Mean CS improved from 1.32 at baseline to 1.40 log units at week 12. VA was stable throughout. Mean CRT decreased from 354 µm at baseline to 332 µm at week 12 (-22 µm, P=0.004). Twenty-six (65%) patients experienced an overall improvement in NEI VFQ-25 score. Interestingly, a correlation was observed between improvement in log CS and CRT change (P=0.000046). CONCLUSION: Contrast sensitivity improved statistically and significantly, and CRT decreased from baseline to week 12 after a switch to aflibercept from ranibizumab. Analysis of CS as an independent outcome end point in neovascular AMD treatment switch studies may provide a more complete understanding of visual response.

Microincisions in cataract surgery.

UNLABELLED: Improvements in phacoemulsification technology and instrumentation and intraocular lens materials and design have enabled cataract surgery to be performed through incisions smaller than 2.0 mm in external width. This evolution has occurred over time, with new challenges arising at each step of the decrease in incision size. This article reviews the current trend of using increasingly smaller incisions to perform phacoemulsification. Specifically, each facet of phacoemulsification is briefly reviewed from a historical context and then evaluated predominantly from a current perspective to better understand the development of the microincision in cataract surgery. The goal is to help the operating surgeon recognize the potential benefits as well as the potential weaknesses of the smaller incision. FINANCIAL DISCLOSURES: Proprietary or commercial disclosures are listed after the references.

An observational study of bimatoprost 0.01% in patients on prior intraocular pressure-lowering therapy: the Canadian Lumigan(®) RC Early Analysis Review (CLEAR) trial.

PURPOSE: To evaluate the ocular hyperemia and intraocular pressure (IOP)-lowering efficacy of bimatoprost 0.01% in subjects with elevated IOP due to primary open-angle glaucoma (POAG) or ocular hypertension (OHT) in a real-world clinical setting. SUBJECTS AND METHODS: This open-label, 12-week, observational study was conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline, week 6, and week 12 using a standardized photographic 5-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes the subgroup of 268 subjects who had been previously treated with latanoprost 0.005%, bimatoprost 0.03%, travoprost 0.004%, and travoprost 0.004% with SofZia™ or nonselective beta-adrenergic receptor blockers prior to the study. RESULTS: After 12 weeks of treatment with 0.01% bimatoprost, ocular hyperemia was graded as none-to-mild hyperemia (grades 0, +0.5, or +1) for 94.1% of subjects and as moderate-to-severe hyperemia (grades +2 or +3) for 5.9%. No statistically significant shifts in ocular hyperemia ratings were observed at week 12 for any of the prior IOP-lowering therapies except bimatoprost 0.03%, in which 20.8% of subjects experienced an improvement. The mean percentage change from baseline IOP at week 12 following the switch to bimatoprost 0.01% monotherapy ranged from -2.3%±17.3% to -26.3%±12.4%. Furthermore, the decreased mean percentage change from baseline IOP was statistically significant across all prior IOP-lowering medications, except for bimatoprost 0.03% at the 6- and 12-week visits and travoprost 0.004% at the 6-week visit. CONCLUSION: This observational study demonstrates that bimatoprost 0.01% was well tolerated among POAG and OHT subjects who switched from prior IOP-lowering medication. Furthermore, a switch in ocular hypertensive treatment to bimatoprost 0.01% was associated with an additional 10%-15% reduction in IOP.

A randomized, prospective study of bimatoprost 0.01% or travoprost/timolol in patients previously treated with latanoprost and timolol to reduce intraocular pressure.

PURPOSE: To compare the efficacy and safety of bimatoprost 0.01% with the fixed combination travoprost 0.004%/timolol 0.5% in subjects with stable intraocular pressure (IOP) control on latanoprost and timolol. METHODS: This was a randomized, prospective, investigator masked, crossover study comparing bimatoprost 0.01% with travoprost/timolol in 40 subjects diagnosed with primary open-angle glaucoma. Subjects were randomized to bimatoprost 0.01% qpm or travoprost/timolol qam and followed for 12 weeks, at which time they were crossed over to the alternate medication and followed for another 12 weeks. Intraocular pressure and hyperemia (rated on a standardized, 5-point photographic scale) were evaluated as change from baseline to 12 weeks following each therapy, and subject preference was elicited at the end of the study. RESULTS: Both treatments were well tolerated and the majority of patients achieved effective IOP control relative to baseline. After 12 weeks of treatment, mean reductions from baseline IOP were -1.68 mmHg OD (right eye) and -1.58 mmHg OS (left eye) with bimatoprost and -0.45 mmHg OD and -0.53 mmHg OS with travoprost/timolol, although the differences between drugs were not statistically significant. Hyperemia scores were significantly higher with the fixed combination of travoprost/timolol than bimatoprost 0.01% as measured at 8 am (both P<0.01). Subject preference at the end of the study was more than 3 to 1 in favor of bimatoprost, with most citing greater tolerability. CONCLUSION: Bimatoprost 0.01% and travoprost/timolol are both effective at reducing IOP in subjects with stable IOP control on latanoprost and timolol, but bimatoprost 0.01% is associated with less hyperemia.

An observational study of bimatoprost 0.01% in treatment-naïve patients with primary open angle glaucoma or ocular hypertension: the CLEAR trial.

BACKGROUND: This study was designed to evaluate the occurrence and severity of ocular hyperemia in subjects with elevated intraocular pressure (IOP) due to primary open angle glaucoma (POAG) or ocular hypertension (OHT) following treatment with bimatoprost 0.01% in a real-world clinical setting. METHODS: This was an open-label, observational study conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% topically as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline and weeks 6 and 12 using a photographic five-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes only the subgroup of 522 subjects who were naïve to IOP-lowering medication prior to the study. RESULTS: After 12 weeks of treatment with bimatoprost 0.01%, hyperemia was graded as none-to-mild (grades 0, +0.5, or +1) for 93.3% of subjects and as moderate-to-severe (grades +2 or +3) for 6.7%. At weeks 6 and 12, most subjects (93.2% and 93.5%) had no change in hyperemia grade from baseline. IOP was reduced by 7.4 mmHg (29.8%) at week 6 and 7.7 mmHg (30.9%) at week 12 from baseline. CONCLUSION: This real-world, observational study found that bimatoprost 0.01% instilled once daily reduced IOP by a mean of 30% from baseline without moderate or severe ocular hyperemia in 93% of treatment-naïve subjects with POAG or OHT.

Twelve-week, randomized, multicenter study comparing a fixed combination of brimonidine-timolol with timolol as therapy adjunctive to latanoprost.

OBJECTIVE: To evaluate the additive intraocular pressure (IOP)-lowering efficacy and safety of fixed-combination brimonidine 0.2%/timolol 0.5% compared with timolol 0.5% at peak and trough effect when used as therapy adjunctive to latanoprost 0.005% in patients with glaucoma or ocular hypertension who require additional IOP lowering. METHODS: In this prospective, randomized, multicenter, investigator-masked, parallel-group study, patients were treated with latanoprost monotherapy for at least four weeks prior to baseline. At baseline on latanoprost, patients with IOP ≥21 mmHg in at least one eye were randomized to twice-daily fixed brimonidine-timolol (n = 102) or timolol (n = 102), each adjunctive to latanoprost for 12 weeks. IOP was measured at 8 am and 10 am at baseline, week 6, and week 12 and evaluated in the per protocol population. The primary efficacy endpoint was peak IOP lowering at 10 am, week 12. Safety measures included adverse events. RESULTS: Baseline mean IOP was similar at 10 am in the treatment groups (brimonidine-timolol 23.4 mmHg; timolol 23.0 mmHg). The mean additional reduction from latanoprost-treated baseline IOP was 8.3 mmHg (35.5%) with fixed brimonidine-timolol and 6.2 mmHg (27.0%) with timolol at 10 am, week 12 (P < 0.001). Patients treated with fixed brimonidine-timolol adjunctive to latanoprost were significantly more likely than patients treated with adjunctive timolol to achieve an IOP <18 mmHg (P = 0.028) and a ≥20% reduction in IOP from baseline (P = 0.047) at both 8 am and 10 am in week 12. Adverse events occurred in 14.7% of fixed brimonidine-timolol patients and 12.7% of timolol patients. Biomicroscopy findings were similar between the treatment groups after 12 weeks of treatment. CONCLUSION: Fixed-combination brimonidine-timolol reduced IOP significantly more effectively than timolol when used as adjunctive therapy to latanoprost in patients with glaucoma and ocular hypertension. Both fixed brimonidine-timolol and timolol were well tolerated as agents adjunctive to latanoprost.

Preoperative cataract grading by Scheimpflug imaging and effect on operative fluidics and phacoemulsification energy.

PURPOSE: To evaluate the power use, chamber stability, and surgical efficiency of a phacoemulsification system when cataracts were graded preoperatively using the Pentacam Nucleus Grading System (PNS) and adjustments were made in phaco parameters based on the cataract grade. SETTING: Royal Victoria Hospital, Barrie, Ontario, Canada. METHODS: Cataracts were graded using Scheimpflug imaging (Pentacam) in consecutive patients. In Group 1, surgery was performed with no change in parameters. In Group 2, adjustments were made preoperatively in fluidics and phaco power to reflect the cataract grade determined by Scheimpflug imaging. Parameters assessed in both groups included effective phaco time (EPT), balanced salt solution (BSS) use, and needle time to remove the cataract. RESULTS: There were 200 patients in each group. Emulsification and aspiration of higher and lower grades of cataract took statistically significantly less EPT and BSS in Group 2 (preoperative parameter adjustments) than in Group 1. The needle time for the higher grades of cataract was statistically significantly less in Group 2. For cataracts of a middle grade (2 to 3; 63% of cases), there was no statistically significant difference between standard phaco settings and adjusted settings. The cataract was effectively aspirated in both groups. CONCLUSION: Preoperatively adjusting phaco parameters based on cataract grade helped improve overall efficiency by reducing the amount of energy and fluid used in the eye and reducing overall phaco time.

Three-month, randomized, parallel-group comparison of brimonidine-timolol versus dorzolamide-timolol fixed-combination therapy.

OBJECTIVE: Fixed combinations of 0.2% brimonidine-0.5% timolol and 2% dorzolamide-0.5% timolol are used to lower intraocular pressure (IOP). The objective of this study was to evaluate the IOP-lowering efficacy and ocular tolerability of brimonidine-timolol compared with dorzolamide-timolol when used as monotherapy or as adjunctive therapy to a prostaglandin analog (PGA) in patients with glaucoma or ocular hypertension. STUDY DESIGN AND METHODS: Pooled data analysis of two randomized, investigator-masked, 3-month, parallel-group studies with identical protocols (ten sites). In all, 180 patients with open-angle glaucoma or ocular hypertension who were in need of lower IOP received topical brimonidine-timolol BID or dorzolamide-timolol BID as monotherapy (n = 101) or as adjunctive therapy to a PGA (latanoprost, bimatoprost, or travoprost) (n = 79). CLINICAL TRIAL REGISTRATION: The studies are registered with the identifiers NCT00822081 and NCT00822055 at http://www.clinicaltrials.gov. MAIN OUTCOME MEASURES: IOP was measured at 10 a.m. (peak effect) at baseline and at months 1 and 3. Tolerability/comfort was evaluated using a patient questionnaire. RESULTS: There were no statistically significant between-group differences in patient demographics. Most patients were Caucasian, and the mean age was 68 years. There were also no statistically significant differences between treatment groups in baseline IOP. At month 3, the mean (SD) reduction from baseline IOP for patients on fixed-combination monotherapy was 7.7 (4.2) mmHg (32.3%) with brimonidine-timolol versus 6.7 (5.0) mmHg (26.1%) with dorzolamide-timolol (p = 0.040). The mean reduction from PGA-treated baseline IOP for patients on fixed-combination adjunctive therapy was 6.9 (4.8) mmHg (29.3%) with brimonidine-timolol versus 5.2 (3.7) mmHg (23.5%) with dorzolamide-timolol (p = 0.213). Patients on brimonidine-timolol reported less burning (p < 0.001), stinging (p < 0.001), and unusual taste (p < 0.001) than patients on dorzolamide-timolol. CONCLUSIONS: Fixed-combination brimonidine-timolol provided the same or greater IOP lowering compared with fixed-combination dorzolamide-timolol. Both fixed-combination medications were safe and well-tolerated. Brimonidine-timolol received higher ratings of ocular comfort than dorzolamide-timolol. The duration of the studies was 3 months, and additional studies will be needed to compare the efficacy and tolerability of brimonidine-timolol and dorzolamide-timolol during long-term treatment.

In vivo digital imaging of the square-edged barrier effect of a silicone intraocular lens.

PURPOSE: To evaluate and compare by high-magnification digital photography the lens epithelial cell (LEC) response and capsule dynamics in vivo after implantation of a square-edged and a round-edged silicone intraocular lens (IOL) in a fellow-eye study. SETTING: Private practice and Royal Victoria Hospital, Barrie, and Soldiers' Memorial Hospital, Orillia, Ontario, Canada. METHODS: After phacoemulsification, a single surgeon implanted a square-edged silicone IOL (SoFlex SE, Bausch & Lomb) in 25 patients who had previously had a conventional round-edged version of the same IOL (SoFlex Li61U, Bausch & Lomb) implanted in their contralateral eye within a 6-week period. SoFlex SE IOL recipients were selected sequentially from those scheduled for surgery within a 3-day period. The IOLs were sequentially photographed 1 week and 1, 3, 6, and 9 months after surgery using magnification of at least x64 through a biomicroscope and a high-resolution digital camera with adapter. Images were transferred to a graphics computer and compared over time. RESULTS: At 1 week, both designs had evidence of LEC migration along the posterior capsule, with the highest cell density around the 6 o'clock position. At 1 month, both IOL designs showed 360 degrees of anterior and posterior capsule adhesion to the edge of the optic. At 1 month, however, migrating LECs encountered a "damming" effect at the square posterior edge but not at the round edge. A thin fibrotic ring began to form around the SoFlex SE edge at 2 months and was complete for 360 degrees at 3 months. At 9 months, there was no evidence of LEC migration beyond this ring. With round-edged IOLs, the fibrotic ring never fully formed and LEC migration continued posterior to the optic. There was a tight capsule shrink-wrap effect with the square-edged IOLs with the fibrotic ring, allowing minimal IOL movement between 1 month and 9 months. The round-edged IOLs tended to decenter and rotate. Anterior capsulorhexis contraction was greater at every time point with the round-edged IOLs than with the square-edged IOLs. CONCLUSION: Early contact inhibition of LECs by a square-edged IOL design and its effects were demonstrated in vivo with sequential, high-resolution digital photography and commercially available graphics software.