Intravitreal bevacizumab for the treatment of choroidal neovascularization associated with pathological myopia

Background: The recent discovery of vascular endothelial growth factor and its role in the pathogenesis of ocular neovascularization has led to the development of new pharmacological agents that could block its action. This study was carried out to investigate the effect of intravitreal injections of bevacizumab on choroidal neovascularization (CNV) associated with pathological myopia.Methods: We retrospectively reviewed the charts of all patients who had CNV secondary to pathological myopia and who had been treated with intravitreally administered bevacizumab between November 2005 and April 2007 at Notre-Dame Hospital in Montréal, Québec. Data on best-corrected visual acuity (BCVA), previous treatments, number of injections, fundus photography, and fluorescein angiography were collected.Results: Ten eyes from 9 patients were followed for a mean period of 9.7 (range 2.5-14) months.At baseline the mean (SD) logMAR BCVA was 0.62 (0.25) (Snellen equivalent 6/24). The mean number of injections per eye was 2.6 (range 1-5). At the end of the study the mean (SD) logMAR BCVA had significantly improved to 0.26 (0.16) (Snellen equivalent 6/10.5; p < 0.001).Vision improved by a mean of 3.9 (range 0-7) lines on the Snellen visual acuity chart. Leakage from the CNV on fluorescein angiography had resolved in 7 of the 10 eyes and was reduced in the 3 other eyes. No drug-related side effects or complications were observed during the follow-up period.Interpretation: Intravitreal injection of bevacizumab appears to be a safe and effective treatment alternative for CNV associated with pathological myopia.     

Triple therapy for neovascular age-related macular degeneration (verteporfin photodynamic therapy, intravitreal dexamethasone, and intravitreal bevacizumab)

Objective: Age-related macular degeneration is a multifactorial disease involving inflammation, neovascularization, and vascular leakage. As a result, a rationale exists for investigating combination treatments that target the different pathological processes involved in this disease. We propose triple therapy consisting of verteporfin photodynamic therapy (PDT), intravitreal bevacizumab, and intravitreal dexamethasone.Design: Retrospective chart review.Participants: Thirty-two eyes of 30 patients were included. None of the patients demonstrated concurrent eye pathology, and none ofthe patients had received previous treatment for their choroidal neovascularization.Methods: One cycle of triple therapy consisted of reduced-fluence PDT (300 mW/cm2 for 83 seconds to deliver 25 J/cm2) followed immediately by an 800 mg (0.08 mL) intravitreal dexamethasone (IVD) injection. At 1 and 7 weeks after PDT and IVD, patients received a 1.25 mg (0.05 mL) bevacizumab injection. At 13 weeks after PDT and IVD, each patient had a repeat optical coherence tomography and fluorescein angiography to assess choroidal neovas-cularization activity. Patients were followed for 12 months.Results: The mean number of treatment cycles was 1.4. The mean number of bevacizumab injections was 2.8. Visual acuity improved from 0.74 (SD 0.33) logMAR (20/100) to 0.53 (SD 0.32) logMAR (20/70) (p > 0.005). Foveal thickness decreased from 328 (SD 116) mm to 216 (SD 85) μm (p > 0.001). Ninety-four percent of patients lost fewer than 3 lines, 31% gained more than 3 lines, and 6% lost more than 3 lines.Conclusions: By combining agents with complementary mechanisms of action, triple therapy could maintain visual acuity and macular anatomy while allowing a reduction in the number of anti-vascular endothelial growth factor injections required.     

Spectral-domain optical coherence tomography (SD-OCT) patterns and response to intravitreal bevacizumab therapy in macular edema associated with branch retinal vein occlusion

Background

To evaluate the baseline spectral-domain optical coherence tomography (SD-OCT) characteristics of macular edema (ME) due to branch retinal vein occlusion (BRVO) for visual outcome after intravitreal bevacizumab injection.

Methods

Fifty-nine patients treated in one eye with intravitreal bevacizumab for ME due to BRVO were retrospectively reviewed. Stepwise multiple regression analysis was used to evaluate the relative contribution of several variables, including SD-OCT characteristics such as photoreceptor inner segment/outer segment (IS/OS) integrity and external limiting membrane (ELM status), baseline best-corrected visual acuity (BCVA), and baseline central retinal thickness (CRT) with final visual outcome.

Results

Thirty-one patients (52.5 %) had disrupted photoreceptor IS/OS integrity. The mean BCVA improved significantly from 0.50 logMAR (20/63 Snellen equivalent) to 0.10 logMAR (20/25 Snellen equivalent) in the intact photoreceptor group (p?=?0.000, paired t-test). However, the mean BCVA was improved in the disrupted photoreceptor group, from 1.10 logMAR (20/252 Snellen equivalent) to 0.94 logMAR (20/174 Snellen equivalent), which was not statistically significant (p?=?0.177, paired t-test). ELM was disrupted in 23 patients (39.0 %). The mean BCVA improved significantly from 0.63 logMAR (20/85 Snellen equivalent) to 0.26 logMAR (20/36 Snellen equivalent) in the intact ELM group (p?=??0.000, paired t-test), however, not significantly improved in the disrupted ELM group, from 1.09 logMAR (20/246 Snellen equivalent) to 1.01 logMAR (20/205 Snellen equivalent) (p?=??0.563, paired t-test). The strongest individual predictor of final BCVA among patients with ME due to BRVO was the integrity of photoreceptor IS/OS layer on SD OCT (r ²?=?0.514, p?=?0.000, stepwise multiple regression), but the most efficient model was the combination of the photoreceptor IS/OS integrity, ELM status, and baseline BCVA (r ²?=?0.671, p?=?0.000, stepwise multiple regression). The strongest predictor of final BCVA was the status of photoreceptor IS/OS integrity (β?=?0.532, p?=?0.000, stepwise multiple regression), followed by ELM status (β?=?0.325, p?=?0.006, stepwise multiple regression), and the baseline BCVA (β?=?0.238, p?=?0.013, stepwise multiple regression).

Conclusion

Our results suggest that baseline SD-OCT characteristics, the status of photoreceptor IS/OS and ELM can be helpful in predicting the final visual outcome after intravitreal bevacizumab injection in these patients.     

Combination therapy in exudative age-related macular degeneration: visual outcomes following combined treatment with photodynamic therapy and intravitreal bevacizumab

Objective: To measure visual outcomes following combined treatment with photodynamic therapy (PDT) and intra-vitreal bevacizumab for exudative age-related macular degeneration (AMD).Design: Single-centre, retrospective cohort analysis.Participants: One hundred and seventy-four eyes in 174 patients, representing a consecutive series of all patients with at least 6 months’ follow-up after combined treatment with PDT and bevacizumab for exudative AMD.Methods: Each patient was treated with PDT, followed by intravitreal injection of bevacizumab approximately 30 minutes later. The patients were then followed at 8-12-week intervals. The primary outcome of the study was the mean change in visual acuity (VA) from baseline.Results: One hundred seventy-four eyes in 174 patients completed at least 6 months’ follow-up, with a mean duration of 10 months. The mean number of treatments was 3.0 for bevacizumab and 1.4 for PDT. After stabilization, the mean treatment-free interval was 193 days, and 52% of the patients did not require postinduction retreatment. Mean VA improved from baseline at 2,4, and 6 months of follow-up (p < 0.05). In the subgroup analysis, treatment-naïve patients had more favorable visual outcomes (p < 0.05).Conclusions: The combination of PDT and intravitreal bevacizumab is an effective therapy for preserving VA in patients with exudative AMD.     

Intravitreal bevacizumab and aqueous shunting surgery for neovascular glaucoma: safety and efficacy

Objective: To study the safety and efficacy of intravitreal injection of bevacizumab followed by aqueous shunting tube surgery for the management of neovascular glaucoma (NVG).Study Design: A prospective, non-randomized study with a historical control group.Participants: Twenty eyes of 20 patients with intractable NVG were treated with intravitreal injection of bevacizumab followed by aqueous shunting surgery (IVB group). A historical group of 10 NVG eyes treated with panretinal photocoagulation followed by aqueous shunting surgery without bevacizumab injection was used for comparison (PRP group).Methods: Injection of bevacizumab (1.25 mg/0.05 mL) was performed under topical anesthesia. An Ahmed valve was implanted in all cases after 1-2 weeks. In the IVB group, 10 eyes received postoperative panretinal photocoagulation (subgroup IA), and 10 eyes were followed without further photocoagulation (subgroup IB). Minimum follow-up was I year or when failure was diagnosed.Results: Mean preoperative intraocular pressure (IOP) was 46.5 mm Hg in the IVB group and 49.2 mm Hg in the PRP group (p = 0.5). After bevacizumab injection, iris neovessels regressed markedly. The final IOP after aqueous shunting tube surgery was 18.8 mm Hg in the IVB group and 15.9 mm Hg in the PRP group (p = 0.2). Postsurgical complications were comparable between the groups. The success rate was 85% and 70% in the 2 groups, respectively. Two eyes were considered failures, and 3 required repeated bevacizumab injections in subgroup IB as compared with I in subgroup IA.Conclusion: Intravitreal bevacizumab is a useful preparatory step to safely and effectively implant an aqueous shunting tube in NVG. Panretinal photocoagulation after bevacizumab injection promotes the success rate of aqueous shunt surgery by permanent ablation of the ischemic retina.     

The effects of intravitreal bevacizumab on patients with macular edema secondary to branch retinal vein occlusion

Objective: To evaluate the effect of intravitreal bevacizumab on visual acuity (VA) and central retinal thickness (CRT) in patients with macular edema (ME) secondary to branch retinal vein occlusion (BRVO).Design: Retrospective review.Participants: The study included 42 patients with ME secondary to BRVO who received intravitreal injections of bevacizumab in 2 referral-based retinal practices in Vancouver, B.C., between November 2005 and July 2006.Methods: We performed a retrospective review of consecutive patients with ME secondary to BRVO. All of the patients in this study had nonischemic BRVOs. Patients were all treated with at least 1 bevacizumab injection and were seen at 6- to 8-week intervals for VA testing. Most of the patients also underwent optical coherence tomography (OCT) 2 months and 6 months after treatment. VA and OCT measurements at each follow-up time point were compared with the baseline values.Results: A total of 42 eyes from 42 patients with ME secondary to BRVO were reviewed. The mean VA improved from 20/280 at baseline to 20/180 at first follow-up session (p < 0.04; average follow-up = 42 days) and remained at a similar level, 20/170, through the eighth follow-up session (p < 0.04; average follow-up = 356). The CRT was reduced from a mean of 451 μm (388-512 μm) at baseline to 358 μm (298-418 μm) at 2 months (p < 0.02) and to 400 μm (335-465 μm) at 6 months postinjection (p < 0.068).Conclusions: We found a significant improvement in VA and CRT in patients with ME secondary to BRVO after intravitreal bevacizumab injection(s). No complications or serious side effects were observed. Intravitreal bevacizumab appears to have an emerging role as either a primary or an adjuvant treatment modality in the setting of ME secondary to BRVO.     

Transconjunctival suturing of the scleral flap for overfiltration with hypotony maculopathy after trabeculectomy

Objective: To assess the efficacy of transconjunctival suturing of the scleral flap in improving hypotony maculopathy resulting from overfiltration after trabeculectomy.Design: Retrospective review.Participants: 35 eyes of 33 patients.Methods: Patients underwent transconjunctival scleral flap suturing for hypotony maculopathy following trabeculectomy using mitomycin C. The scleral flap was sutured through the conjunctiva as an outpatient clinic procedure using a spatulated needle with a 10-0 nylon suture.Results: The average age of the patients was 67.5 (SD 4.80, range 39-83) years, and 52% patients were male. The average duration of hypotony prior to transconjunctival suturing of the flap was 108.0 (SD 68.3) days. The median intraocular pressure (IOP) before suturing was 3 mm Hg, and the median IOP 6 months after the procedure was 9 mm Hg (p < 0.0001). The median best-corrected visual acuity (BCVA) before transconjunctival suturing of the scleral flap was 20/100, and the median BCVA 6 months after the procedure was 20/30 (p < 0.0001). Compared with visual acuity before suturing the average gain in BCVA was 4.9 (SD 0.8) lines.Conclusions: Transconjunctival suturing of the trabeculectomy scleral flap is an effective treatment to raise IOP and improve visual loss from hypotony maculopathy after trabeculectomy with overfiltering blebs.     

Incidence and characteristics of acute intraocular inflammation after intravitreal injection of bevacizumab: a retrospective cohort study

Objective: To determine the incidence and characteristics of acute intraocular inflammation after intravitreal bevacizumab injections from a tertiary care retinal practice.Design: Retrospective cohort study.Participants: A consecutive series of patients who had received bevacizumab injections performed by a single surgeon.Methods: We reviewed the records of all patients with severe anterior chamber inflammation and (or) vitritis after bevacizumab injections.Results: A total of 693 bevacizumab injections were performed on 193 eyes of 173 patients between June 2006 and March 2008. There were a total of 9 cases of acute intraocular inflammation for an incidence of 1.30% (95% CI: 0.69%-2.47%). All patients had a worse visual acuity at the end of follow-up than on injection day. The mean loss of vision was 6.1 lines of Snellen visual acuity; one patient developed inflammation-induced glaucoma which required surgical intervention.Conclusions: Intravitreal injection of bevacizumab is associated with a low but significant risk of acute intraocular inflammation and may result in significant visual loss.     

Visual acuity after intravitreal triamcinolone for diabetic macular edema refractory to laser treatment: A meta-analysis

Objective: To quantify the effect on visual acuity of intravitreal triamcinolone for the treatment of laser-refractory diabetic macular edema (DME).Study Design: Meta-analysis of eligible studies identified by searching MEDLINE, EMBASE, the Cochrane Library, and Google.Participants: 7 randomized controlled trials and 3 cohort studies.Methods: A search of the literature between 1950 and September 2008 identified 540 articles. Studies that evaluated the efficacy of triamcinolone for the treatment of DME refractory to laser photocoagulation, reported visual acuity data, and compared the intervention with an appropriate control group were included. Exclusion criteria were studies of non-DME, triamcinolone used as an adjunct to another treatment, and triamcinolone delivery other than intravitreally.Results: Using a random-effects model, there was a statistically significant summary mean difference in visual acuity of −0.3 13 logarithm of the minimum angle of resolution (logMAR) units (95% CI −0.55 1, −0.074) after 1 month of follow-up. This difference declined to −0.125 logMAR units (95% CI −0.181, −0.070) by 3 months and to −0.043 logMAR units (95% CI −0.090, 0.003) by 6 months. No evidence of publication bias was present. There was a high level of heterogeneity in this group of studies (meta-analysis of 1-month follow-up data: Q-statistic = 21.987, p < 0.001), attributable primarily to study design.Conclusions: These meta-analyses demonstrate that intravitreal triamcinolone results in a temporary improvement of visual acuity in patients with laser-refractory DME, with a peak benefit of approximately 3 lines of visual acuity 1 month postinjection.     

Comparison of observation, intravitreal bevacizumab, or pars plana vitrectomy for non-proliferative type 2 idiopathic macular telangiectasia

Purpose

To compare visual and anatomic outcomes in eyes with type 2 idiopathic macular telangiectasia (Mactel) treated with either intravitreal bevacizumab (IVB), observation, or pars plana vitrectomy (PPV) with internal limiting membrane removal.

Methods

Retrospective, consecutive, interventional case series of phakic patients with Mactel. Best-corrected Snellen visual acuity (BCVA) and complete ophthalmic exam was obtained prior to treatment and at subsequent 3-month intervals for a minimum of 6 months. Fluorescein angiographic and spectral-domain optical coherence tomography features were examined, and compared to BCVA at treatment initiation and follow-up.

Results

Fifty-six eyes of 28 patients were evaluated. Mean age was 65?±?12 years, and mean follow-up was 24?±?13 months. Patients were treated with either observation (n?=?33), IVB (n?=?15), or PPV (n?=?8). Mean number of treatments for the IVB group was 2.5?±?3.5 intravitreal injections. No significant differences in BCVA change were observed between treatment groups via one-way ANOVA (p?=?0.49). Presence of inner retinal cysts was not correlated to BCVA (p?>?0.05). Discontinuous outer nuclear layer was significantly related to worse initial and final vision, but not to BCVA change.

Conclusion

IVB and PPV with ILM removal appear ineffective in improving visual outcome in eyes with non-proliferative Mactel. SD-OCT evidence of disrupted foveal outer nuclear layer is related to decreased BCVA, but not related to BCVA change following treatment.     

Behçet's disease: comparing 3 decades of treatment response at the National Eye Institute

Background: The goal of the present study was to analyze differences in response to the treatment of ocular Behçet's disease (BD) in the 1960s, 1980s, and 1990s.Methods: Medical records of 120 patients with uveitis due to BD followed at the National Eye Institute, National Institutes of Health, from 1962 to 2004, were reviewed.Results: The patients were categorized into 3 groups according to the time of follow-up: the first group was followed from 1962 until 1972, the second group from 1983 until 1992, and the third group from 1992 through 2004. Snellen visual acuity was converted to logMAR values. The range of values for inflammation was 0.5 (trace), 1 (mild), 2 (moderate), and 3 (severe). There were 45 patients (89 affected eyes) in the 1960s group, 26 patients (52 eyes) in the 1980s group, and 49 patients (94 eyes) in the most recent group. Statistical analysis showed that the mean logMAR score decreased with each decade. Mean visual acuity in the 1990s group was significantly better than in the previous decades (p < 0.001 for the 1960s group and p = 0.019 for the 1980s). The mean inflammation score was significantly higher in the 1960s than in the subsequent decades (p < 0.001 both for the 1980s and for the 1990s).Interpretation: BD is a severe, blinding disorder. There was a definitive trend toward improvement in clinical outcome from the 1960s to 1990s. We attribute this trend to the introduction of newer, more potent corticosteroid-sparing agents and targeted therapy.     

Intravitreal bevacizumab in the treatment of vasoproliferative retinal tumours

Aim

To evaluate the efficacy of intravitreal bevacizumab in the treatment of retinal vasoproliferative tumours (VPT).

Materials and Methods

Six eyes of 6 patients with VPT who received intravitreal bevacizumab were retrospectively reviewed. All patients received between one and three injections of intravitreal bevacizumab depending upon response to treatment. Best-corrected visual acuity (BCVA), tumour size, and presence of co-pathology or sequelae were noted pre- and postoperatively and then analysed. Subsequent retreatments were performed in patients with recurrent or persistent VPT according to the ophthalmologist''s discretion. Retreatments included photodynamic therapy with verteporfin, ruthenium-106 plaque brachytherapy, or endoresection of tumour.

Results

The mean follow-up duration was 33.3 months (range 10–66 months). At baseline, the mean logMAR BCVA was 1.45 (Snellen equivalent of 6/165); range 0.10–1.90 (6/8—CF). Following bevacizumab treatment the mean logMAR BCVA was 0.98 (Snellen equivalent of 6/57); range 0.5–1.9 (Snellen equivalent of 6/19 to CF). Therefore, there was no statistically significant change in visual acuity. The mean tumour thickness reduced from 2.4 to 2.1 mm following treatment with bevacizumab. However, this did not reach the statistical significance of P<0.05. Despite the visual improvement following bevacizumab therapy, five out of six patients had recurrence of tumour activity during the follow-up period and required further intervention in order to achieve sustained regression.

Conclusions

Intravitreal bevacizumab appeared to result in temporary reduction of tumour thickness in 3 out of 6 VPT patients. However, neither the reduction in tumour thickness nor the change in visual acuity were statistically significant and intravitreal bevacizumab monotherapy had limited effectiveness in causing long-term regression of the lesions. Additional therapy was indicated in five out of six patients to establish long-term regression. The efficacy of bevacizumab as an adjunct is as yet undetermined and further studies are needed. Presently, we recommend other treatment modalities in the long-term management of VPTs.     

Can preoperative anterior chamber angle width predict magnitude of intraocular pressure change after cataract surgery?

Objective: To determine whether preoperative anterior chamberangle width,capturedbyanteriorsegment optical coherence tomography (AS-OCT), can be a predictor of intraocular pressure (IOP) change following cataract surgery.Design: Prospective comparative observational study.Participants: Fifty-three eyes of 53 patients awaiting cataract surgery were included.Methods: Measurement of anterior chamber angle width and IOP using AS-OCT and Goldmann’s applanation tonometry, respectively, were performed before and 6 months after phacoemulsification and intraocular lens implantation. Preoperative and postoperative measurements were compared using paired t test. The prediction rule defined success as ≥20% IOP reduction from the baseline preoperative IOP measurement. Multivariate regression analysis was performed to assess the association of postoperative IOP with independent variables, including age, sex, systemic hypertension, diabetes mellitus, glaucoma, and preoperative anterior chamber angle width.Results: Data were collected from 32 females and 21 males with visually significant cataract. Mean age was 73.3 (SD 8.2) years. Mean IOP dropped from 15.1 (SD 3.l)mm Hg to 12.8 (SD 2.5) mm Hg (p < 0.0001) after cataract extraction. Mean anterior chamber angle width increased from 24.7° (SD 7.1°) to 38.1° (SD 6.0°) after surgery (p < 0.001). Multivariate regression analysis did not identify preoperative variables to be significantly associated with ≥20% postoperative IOP reduction.Conclusions: Cataract surgery results in significant and sustained mean reductions in IOP and concurrent increases in anterior chamber angle width for a period of at least 6 months after surgery. However, measurements of the preoperative anterior chamber angle width did not predict the IOP-lowering effect of cataract surgery.     

Visual acuity measured with a smartphone app is more accurate than Snellen testing by emergency department providers

Purpose

To assess the accuracy of best-corrected visual acuity (BCVA) measured by non-ophthalmic emergency department (ED) staff with a standard Snellen chart versus an automated application (app) on a handheld smartphone (Paxos Checkup, San Francisco, CA, USA).

Methods

The study included 128 subjects who presented to the Stanford Hospital ED for whom the ED requested an ophthalmology consultation. We conducted the study in two phases. During phase 1 of the study, ED staff tested patient BCVA using a standard Snellen test at 20 feet. During phase 2 of the study, ED staff tested patient near BCVA using the app. During both phases, ophthalmologists measured BCVA with a Rosenbaum near chart, which was treated as the gold standard. ED BCVA measurements were benchmarked prospectively against ophthalmologists’ measurements and converted to logMAR.

Results

ED logMAR BCVA was 0.21 ± 0.35 (approximately 2 Snellen lines difference ± 3 Snellen lines) higher than that of ophthalmologists when ED staff used a Snellen chart (p?=?.0.00003). ED BCVA was 0.06 ± 0.40 (less than 1 Snellen line ± 4 Snellen lines) higher when ED staff used the app (p?=?0.246). Inter-observer difference was therefore smaller by more than 1 line (0.15 logMAR) with the app (p?=?0.046).

Conclusions

BCVA measured by non-ophthalmic ED staff with an app was more accurate than with a Snellen chart. Automated apps may provide a means to standardize and improve the efficiency of ED ophthalmologic care.

     

Satisfaction and dysphotopsia in the pseudophakic patient

Objective: To examine factors that influence satisfaction after uncomplicated cataract surgery.Design: Retrospective case review and examination of patients.Participants: Sixty-one consecutive patients, seen at the John A. Moran Eye Center, University of Utah School of Medicine, who had uncomplicated cataract surgery from 1 practice and 40 consecutive control patients who met the inclusion criteria and were willing to participate.Methods: Inclusion criteria were best-corrected visual acuity (BCVA) of at least 20/20, without any ocular disease that might affect vision. Patients were given a complete ophthalmic examination, had photos of the intraocular lens (IOL) and capsule taken, and were asked questions about dysphotopsia and satisfaction. A group of patients >65 years old with 20/20 BCVA and without other ophthalmic diagnoses were recruited, asked the same questions, and compared.Results: The only significant correlation with dissatisfaction was dysphotopsia (r = 0.602, CI 0.42-0.74, p < 0.0001). BCVA, uncorrected visual acuity, posterior capsular opacification, and anterior capsule overlap of the optic were not significantly correlated. The IOL patients were significantly worse for reported glare (p < 0.0001), photophobia (p < 0.0001), and flashes of light (p = 0.0002), but not for halos.Conclusions: While satisfaction with cataract removal and IOL placement is high, dysphotopsia is the most important contributor to dissatisfaction and is relatively common. Furthermore, these symptoms are much worse than in age-matched controls. Research seeking to ameliorate dysphotopsia is clinically important.     

Testing toxicity of multiple intravitreal injections of bevacizumab in rabbit eyes

Objective: To evaluate the potential toxicity of repeated intravitreal injections of bevacizumab in rabbit eyes.Design: Randomized, placebo-controlled experimental animal study.Participants: Fourteen chinchilla rabbits; 12 assigned to the experimental group and 2 assigned to the normal control group.Methods: Three sequential, biweekly, intravitreal injections of bevacizumab in doses of 2.5 mg/0.1 mL or 5.0 mg/0.2 mL were performed on each rabbit. Evaluations included intraocular pressure (IOP), aqueous flare, B-scan ultrasound, fundus photography, ultrasound biomicroscopy, electroretinography (ERG), and visually evoked potentials (VEPs) performed at baseline and during the follow-up period. The eyes were enucleated at 1 week and 4 weeks after the last intravitreal injection, and underwent light and electron microscopic evaluations, as well as testing for apoptotic activity.Results: After intravitreal injections, no changes were found by regular clinical observation and IOP tests. There was no significant difference in the anterior chamber inflammatory activity evaluated by the laserflare meter. No evidence of retinal toxicity was seen after intravitreal bevacizumab at doses of 2.5 and 5.0 mg by either ERG or flash VEPs. Electron microscopy did show the presence of inflammatory cells and some ultrastructural changes in the photo-receptor cells in the 5.0 mg experimental group 1 week after the third injection. Mild to moderate apoptosis of photoreceptors was detected in the 5.0 mg group at the same time.Conclusions: The biweekly, multiple intravitreal injections of bevacizumab did not result in evidence of toxicity in regular clinical and functional observations at both 2.5 mg and 5.0 mg doses. The 5.0 mg dose may induce transient inflammation, ultrastructural abnormalities, and apoptosis.     

Concept of a functional retinal locus in age-related macular degeneration

Purpose: Preferred retinal loci used for eccentric fixation in patients with age-related macular degeneration (AMD) may be different from the eccentric neighbouring loci of highest retinal sensitivity. This study was designed to highlight the conceptual difference between the 2 and the concept of a functional retinal locus encompassing both the preferred retinal locus and the locus with highest retinal sensitivity.Design: Prospective, nonrandomized, observational case series.Participants: We recruited 15 adults with documented AMD, low vision, and best-corrected visual acuity of 20/50-20/400 in the better eye.Methods: Automated microperimetry methods were used to assess topographic retinal sensitivity and location of preferred retinal loci.Results: Mean (SD) age for the group was 85.1 (6.5) years. Mean (SD) best-corrected visual acuity measured was 0.88 (0.25) logMar units (20/150). The mean (SD) eccentricity of the preferred retinal locus used forfixation was different from the eccentricity of the area with highest retinal sensitivity in the same eye (7.53° [2.47°] vs 9.30° [2.93°], respectively; p < 0.0003). The oculomotor efficiency score measured 82%. The mean (SD) retinal sensitivity at the preferred retinal loci was inferior to that of loci with highest retinal sensitivity (5.83 [4.26] vs 8.60 [3.06] dB, respectively; p < 0.0007). The highest correlation was measured between potential visual acuity estimates and estimates of retinal sensitivity at the highest retinal sensitivity loci (p < 0.0048).Conclusions: Preferred retinal loci and highest retinal sensitivity loci are not identical in AMD cases. A new concept of functional retinal locus is proposed to define their relation. A new concept of an oculomotor efficiency score is proposed to define oculomotor abilities when macular function is lost.     

Improvement of visual acuity based on optical coherence tomography patterns following intravitreal bevacizumab treatment in patients with diabetic macular edema

AIM:To report the visual outcome based on various patterns of optical coherence tomography (OCT) morphology in diabetic macular edema (DME), following treatment with anti-VEGF intravitreal bevacizumab (IVB) injection.METHODS:Sixty-seven consecutive subjects with centre involving DME underwent intravitreal injection of Bevacizumab (1.25 mg/0.05 mL) in this retrospective, comparative, non randomized study. The DME was classified into one of four categories:focal, diffuse, focal cystoid and neurosensory detachment based on OCT. Best corrected visual acuity (BCVA), macular appearance, and OCT findings were used to decide whether the subject should have a repeat injection of intravitreal bevacizumab. Outcome measures were a change in mean BCVA (Snellen converted to logMAR) and central macular thickness (CMT) in each group during the six month follow-up period.RESULTS:The mean BCVA improved to logMAR 0.23 at final follow-up from a baseline of 0.32 logMAR (P=0.040) in the focal group, logMAR 0.80 at final follow-up from a baseline of 0.82 logMAR (P=0.838) in the diffuse group, worsened to logMAR 0.53 at final follow-up from a baseline of 0.43 logMAR (P=0.276) in the focal cystoid group, and improved to logMAR 0.79 at final follow-up from a baseline of 0.93 logMAR (P=0.490) in the neurosensory detachment group. The mean CMT before treatment were 298.8±25.03 μm in the focal group, 310.8±40.6 μm in the diffuse group, 397.15±31.05 μm in the focal cystoid group and 401.03±75.1 μm in the neurosensory detachment group. A mean of 2.05 (range:1-5) injections in the focal group, 1.32 (range:1-2) in the diffuse group, 2.6 (range:1-6) in the focal cystoid group and 2.6 (range:1-6) in the neurosensory detachment group were performed during the six month follow-up period. Following intravitreal bevacizumab treatment, vision improved, remained unchanged or worsened in 11, 7 and 2 subjects in focal group; 11, 9 and 8 in diffuse group; 0, 2 and 4 in focal cystoid group and 5, 5 and 3 subjects respectively in neurosensory detachment group.CONCLUSION:OCT morpholgy patterns in DME may predict the effects of intravitreal bevacizumab treatment, and patients with focal DME are most likely to benefit from the improvent of visual acuity from this treatment.     

Changes in wave-front aberrations after rigid gas permeable contact lens fitting in post—laser in situ keratomileusis patients with visual complaints

Objective: To evaluate the effect of rigid gas permeable (RGP) contact lenses in reducing wave-front aberrations in post-laser in situ keratomileusis (LASIK) myopic patients.Design: Cross-sectional study.Participants: Thirty patients with visual complaints after conventional LASIK procedure for correcting myopia.Methods: The 30 patients were fitted with RGP contact lenses. Wave-front measurements were taken before and after RGP contact lens wearing.Results: Compared with bare eye examinations, root mean-square values of higher-order aberrations (HOAs) significantly decreased with RGP contact lens use. Amongthese, spherical aberration decreased from 0.507 (SD 0.304) μm to 0.164 (SD 0.121) μm(t = 7.186, p < 0.001); coma decreased from 0.470 (SD 0.312) μm to 0.165 (SD 0.090) μm (t = 5.566, p < 0.001); secondary coma decreased from 0.079 (SD 0.050) μm to 0.044 (SD 0.027) μm (t = 4.118, p < 0.001); and total HOAs decreased from 0.782 (SD 0.449) μm to 0.307 (SD 0.140) μm (t = 6.710, p < 0.001).Conclusions: Fitting RGP contact lenses effectively decreased HOAs induced by conventional myopic LASIK surgery. Possible reasons may be the elimination of irregularity and dissymmetry on the corneal anteriorsurface, relief of the aspherical extent of the central corneal surface, and enlargement of the effective optical zone.     

Identifying systemic safety signals following intravitreal bevacizumab: systematic review of the literature and the Canadian Adverse Drug Reaction Database

Objective: As the off-label use of intravitreal bevacizumab continues for an increasing number of ocular conditions, a systematic review of the literature aimed at detecting temporally associated systemic adverse events was undertaken.Design: Systematic review of the literature and a health regulatory database.Participants: A total of 22 different clinical studies representing 12 699 patientsMethods: A systematic review indexed by Ovid MEDLINE, EMBASE, ISI Web of Science, the Cochrane database (CENTRAL), and the Canadian Adverse Drug Reaction Information System Database was performed. All clinical studies with at least 100 eyes injected with bevacizumab and case reports documenting suspected events were included for review.Results: A total of 22 different clinical studies were reviewed, including an international internet survey, 6 retrospective studies assessing the safety of intravitreal bevacizumab, and 15 clinical trials. The most common adverse systemic event reported in these studies, representing 12 699 patients was an increase in blood pressure (0.46% of patients), followed by cerebrovascular accidents (0.21% of patients), and myocardial infarction (0.19% of patients). The 6 case reports documented suspected events not previously identified and only 1 systemic event from the Health Canada database was retrieved.Conclusions: The systemic events temporally associated with intravitreal bevacizumab are mainly of cardiovascular and neurological origin and can be predicted from an exaggerated pharmacology, although a causal association cannot be established at this time. Health Canada's spontaneous drug reporting system is an underutilized resource and a more active surveillance system such as a patient registry may be better suited to establish the low rates of systemic adverse events following bevacizumab use in ophthalmology.