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.     

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.     

Intravitreal bevacizumab (avastin) for subfoveal neovascular age-related macular degeneration

Objective To report the visual and anatomic outcome of intravitreal bevacizumab (Avastin) injections in the treatment of subfoveal neovascular age-related macular degeneration (AMD). Methods Interventional, consecutive, retrospective case series. Sixty-five eyes of 65 patients with subfoveal neovascular age-related macular degeneration (AMD) received three intravitreal bevacizumab (1.25 mg) injections. Outcome measures included visual acuity (VA), central retinal thickness (CRT), and size of lesion at 24 or more weeks follow-up. Results Thirty-five eyes had prior treatment with photodynamic therapy (PDT). At presentation, VA was 1.12 ± 0.62 logMAR, CRT was 305 ± 115 μm, and greatest linear diameter (GLD) of the lesion was 4,902 ± 1,861 μm. There was no statistically significant difference between previous PDT and naïve eyes in VA, CRT, and GLD at presentation. After three bevacizumab injections, VA, CRT, and GLD significantly improved (P < 0.0001 in all groups). There was no statistically significant difference between CRT and GLD outcomes and subfoveal neovascular membrane type or age. Eyes with better VA at baseline and without previous PDT treatment achieved better final VA (P < 0.0001 and P = 0.045, respectively). A classic membrane type and lower age were somewhat associated with better post-treatment VA. Conclusions Short-term results suggest that intravitreal bevacizumab is well tolerated and associated with improvement in VA, decreased CRT, and decreased lesion size in most patients. The most important predictors of final VA outcomes were baseline VA and no previous PDT treatment. Further evaluation of intravitreal bevacizumab for the treatment of subfoveal neovascular AMD is warranted.     

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.     

Beyond visual acuity: functional outcome and patient satisfaction following treatment for age-related macular degeneration

Objective: The success of current medical treatments for choroidal neovascular membranes secondary to age-related macular degeneration (AMD) has often been determined anatomically by change in lesion size and cessation of leakage. Measuring the functional success of treatments has most often revolved around visual acuity and has seldom encompassed patients'; satisfaction with treatment. Using additional objective and subjective measures to assess the outcome of treatments may provide greater insight into the visual functions that are lost, maintained, or improved during the course of treatment.Study Design: Cross-sectional study.Participants: Forty-six patients diagnosed with exudative AMD. Participants had received at least 1 photodynamic therapy (PDT) treatment at the time of testing (mean 3.0, SD 1.9)Methods: Objective tests of visual function (Snellen, Early Treatment Diabetic Retinopathy Study, Minnesota Low-Vision Reading Test, Contrast Sensitivity, Face Acuity) and a subjective questionnaire, the Visual Function-14 (VF-14) were administered to all patients. Treating ophthalmologists completed a 3-item questionnaire.Results: No objective measures of visual function correlated with patient satisfaction or with the ophthalmologists'; evaluation of treatment success. The VF-14 was not related to the ophthalmologists'; evaluation of treatment outcome. Similarly, patient satisfaction was unrelated to the ophthalmologists'; assessment of treatment success. A correlation was found between the VF-14 and patient satisfaction, r = 0.50, p < 0.05.Conclusions: Objective measures of visual function do not necessarily reflect the viewpoint of patients regarding PDT treatment outcome. Patients and doctors differ in their interpretation of treatment success and patients'; overall satisfaction might best be reflected through a visual function questionnaire.     

Outcome of intravitreal bevacizumab for idiopathic choroidal neovascularization in a Chinese population

Objective: To assess the long-term visual and anatomical outcomes and safety of intravitreal injection of bevacizumab for idiopathic choroidal neovascularization (ICNV) in Chinese patients.Design: Retrospective interventional case series.Participants: Seventy-seven eyes of 77 patients with ICNV.Methods: Patients were given intravitreal injection of bevacizumab (1.25 mg/0.05 mL) for ICNV between March 2006 and May 2008. Main outcome measures were changes in best-corrected visual acuity (BCVA), central foveal thickness, which was measured by optical coherence tomography, and fluorescein angiography findings.Results: Mean follow-up was 14.3 (SD 2.4, range 10∼20) months. Mean BCVA improved from 0.66 (SD 0.36) logMAR at baseline to 0.25 (SD 0.28) logMAR at final follow-up (p < 0.001). Sixty-one patients (79%) gained BCVA of ≥2 Snellen lines, and 1 eye (1%) lost BCVA of ≥2 Snellen lines. Mean central foveal thickness decreased from 365 (SD 124) μm at baseline to 211 (SD 94) μm at final visit (p < 0.001). Sixty-two eyes (81%) needed reinjection. Both BCVA improvement and the change in central foveal thickness between the 1 — time injection group and the multi-injections group were not statistically significant (p = 0.45 and p = 0.19, respectively). No significant ocular or systemic adverse effects were observed.Conclusions: The long-term results suggest an encouraging efficacy and safety of intravitreal bevacizumab for ICNV in Chinese patients.     

Photodynamic therapy combined with intravitreal bevacizumab and sub-tenon triamcinolone acetonide injections for age-related macular degeneration

Purpose

To report the results of triple therapy with photodynamic therapy (PDT) (PDT combined with intravitreal injection of bevacizumab (IVB) and sub-tenon injection of triamcinolone acetonide (STTA)) for the treatment of age-related macular degeneration (AMD) in Japanese patients.

Methods

This retrospective case series included 38 eyes of 38 patients with exudative AMD treated with PDT combined with IVB (1.25 mg) and STTA (40 mg). Retreatment was performed in the same manner with intervals of at least 3 months. All patients had been treatment naïve, with a follow-up period of 12 months. Best-corrected visual acuity (BCVA), macular retinal thickness (MRT) on optical coherence tomography, and the number of treatments were analyzed.

Results

The mean logarithm of the minimum angle of resolution BCVA in patients treated with PDT triple therapy was 0.86 ± 0.55 at baseline and 0.62 ± 0.55 at 12 months (p < 0.001). The mean MRT was 554.0 ± 202.6 μm at baseline and 205.1 ± 78.6 μm at 12 months (p < 0.001). During the 1-year follow-up, the average number of PDT triple therapy (treatments per patient) was 1.1. No complications, for example increase in intraocular pressure, cataract, or endophthalmitis, were observed.

Conclusions

In AMD patients, PDT triple therapy significantly improved visual acuity with a minimum number of treatments and a low risk of complications during the 1-year follow-up.

     

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.     

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.     

Potential for 2 priority systems to be used as appropriateness of indication tools for cataract surgery

Objective: To test 2 systems developed to prioritize patients on waiting lists for cataract surgery, the Western Canadian Waiting List (WCWL), and the Catalan Agency for Health Technology Assessment and Research Cataract Priority System (CCPS), as tools for judging the appropriateness of the intervention.Design: Cross-sectional study with follow-up.Participants: A total of 1723 prospective patients awaiting cataract extraction in 5 hospitals were included in the study. Methods: Priority scores using the WCWL and the CCPS systems were calculated and compared with visual acuity (VA) and visual function, measured by the Visual Function-14 index, before and after surgery. The sensitivity of each priority system to different groups was evaluated using a validated appropriateness of indications tool for cataract extraction. One-way analysis of variance and the Jonckheere-Terpstra test were used to detect differences in group scores. Spearman correlation coefficients were also examined.Results: The WCWL and CCPS systems produced different mean values according to the preoperative levels of VA and visual function (p < 0.0001). Neither system showed a significant difference in mean scores based on gains in VA and visual function. Both systems produced different mean scores according to the different groups of appropriateness set by the appropriateness of indications tool for cataract (p < 0.0001).Conclusions: Given that appropriateness tools should correlate with outcomes, we recommend using neither the WCWL nor the CCPS for appropriateness purposes. Incorporating new criteria into these systems may improve the correlation with important outcomes and their adequacy for use as appropriateness tools.     

Intravitreal bevacizumab for iris neovascularization following proton beam irradiation for choroidal melanoma

Objective: To evaluate the safety and efficacy of intravitreal injections of bevacizumab as an eye-sparing treatment for iris neovascularization (NVI) following proton beam irradiation for choroidal melanoma.Design: Retrospective interventional case series.Participants: Four patients who received intravitreal bevacizumab for NVI following proton beam irradiation for choroidal melanoma were identified in the Department of Ophthalmology archives at the University of British Columbia. Methods: Clinical details were reviewed. Long-term follow-up of more than 2 years was detailed for each case.Results: All 4 patients responded to a single injection of bevacizumab with regression of NVI. Neovascular glaucoma (NVG) was evident in 3 cases, 2 of which had stable intraocular pressure following treatment. NVI recurred following a single injection in all patients after an interval ranging from 1 month to 12 months. A longer period of regression was seen in patients with fewer systemic neovascular risk factors and earlier treatment.Conclusions: Regression of NVI following proton beam irradiation for choroidal melanoma was seen in all treated patients. Repeated treatments may be required to maintain regression of new vessels. This treatment modality may be a useful eye-sparing adjunct in the prevention and treatment of NVG following proton beam irradiation.     

Two-year results of combined intravitreal anti-VEGF agents and photodynamic therapy for retinal angiomatous proliferation

Purpose

To clarify the efficacy of a combination of intravitreal anti-vascular endothelial growth factor (VEGF) injections and photodynamic therapy (PDT), over 24 months, for patients with symptomatic retinal angiomatous proliferation (RAP).

Methods

We retrospectively reviewed 13 treatment-naïve eyes of 12 patients (7 men, 5 women; age range (mean), 63–92 (77) years) treated with intravitreal bevacizumab (IVB) plus PDT as initial treatment. Retreatment was performed with IVB plus PDT until February 2009 or intravitreal ranibizumab and PDT from March 2009.

Results

Mean best-corrected visual acuity (BCVA) significantly improved from 0.26 at baseline to 0.40 at 24 months (P = 0.013). The mean improvement in BCVA at 24 months from baseline was 1.79 lines. The central retinal thickness decreased significantly from 431 to 142 microns at 24 months (P < 0.0001). Complete occlusion of the retinal–retinal anastomosis was achieved in seven of the 10 eyes at 24 months. The mean number of PDT treatments during 24 months was 2.8 and the mean number of injections was 3.4. Geographic atrophy was seen in four eyes without significant decline of VA at 24 months.

Conclusion

Combined anti-VEGF and PDT for RAP patients effectively maintained or improved VA and reduced exudation, without severe adverse events, over 24 months.     

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.     

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.     

Effekt von Bevacizumab auf die Abhebung des retinalen Pigmentepithels bei okkulter choroidaler Neovaskularisation

Purpose

This study aimed to investigate the effect of bevacizumab on pigment epithelial detachment (PED) in occult choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) and to determine predictive factors.

Methods

73 eyes of patients with AMD and PED due to CNV with subretinal and/or intraretinal fluid were assessed. Patients were treated with 1.25 mg of intravitreal bevacizumab.

Results

After 30.6 weeks, the mean visual acuity (VA) increased from 0.53 to 0.49 logMAR (p=0.170). The mean PED height decreased from 354.4 μm to 277.4 μm (p=0.004). Although 53.4% of the eyes showed a reduction in PED, this did not correlate with a significant change in VA. Predictive factors were a high baseline PED and VA <0.32.

Conclusion

Half of the patients showed PED flattening. Especially in patients with distinctive PED, a response to intravitreal bevacizumab may be expected. This therapy can stabilize VA, but PED flattening does not essentially correlate with an increase in VA.     

Pharmacogenetic Influence of LOC387715/HTRA1 on the Efficacy of Bevacizumab Treatment for Age-Related Macular Degeneration in a Korean Population

Purpose

The purpose of this study was to determine the pharmacogenetic effects of complement factor H (CFH) Y402H, LOC387715 and high-temperature requirement factor A1 (HTRA1) genotypes on the treatment of exudative age-related macular degeneration (AMD) by intravitreal bevacizumab injection in a Korean population.

Methods

Seventy-five patients diagnosed with exudative AMD were treated with intravitreal bevacizumab (2.5 mg) monotherapy. All patients received three initial intravitreal bevacizumab injections every four weeks and were then treated "as needed" based on clinical findings, optical coherence tomography and fluorescein angiography during the 12 month follow-up period after the third injection.

Results

The difference in visual acuity improvement among the three genotypes of LOC387715 were statistically significant at six months post-treatment (logarithm of the minimum angle of resolution; TT, 0.346; GT, 0.264; GG, 0.188; p = 0.037). Among the LOC387715 genotypes, the number of additional injections was lower in patients who had the risk T allele (GG, 2.143; GT, 2.000; TT, 1.575; p = 0.064). There was no significant difference between visual acuity and central macular thickness change in the CFH Y402H polymorphism group during the 12 month follow-up period. However, the TC group of CFH Y402H required more additional bevacizumab injections than the TT group (TT, 1.517; TC, 3.363; p = 0.020).

Conclusions

This study demonstrated that different LOC387715/HTRA1 genotypes resulted in different bevacizumab treatment responses on exudative AMD. Patients with the risk allele had an improved treatment response and less need for additional injections. However, patients with the CFH Y402H risk allele needed more additional injections of bevacizumab in order to improve visual acuity. This study illustrates how pharmacogenetic factors may help determine treatment modality and dosing. This could ultimately provide basic data for ''personalized medicine'' in AMD.     

Low-fluence photodynamic therapy combinations in the treatment of exudative age-related macular degeneration

AIM: To compare the efficacy of low-fluence photodynamic therapy (PDT) combinations in the treatment of age-related macular degeneration (AMD). METHODS: Forty-five previously untreated eyes of 45 patients with exudative AMD whose best-corrected visual acuity (BCVA) was ≥0.3 (Snellen) were enrolled. 15 patients in Group I underwent low-fluence PDT (25J/cm2-300mW/cm2-83sec) and intravitreal pegaptanib combination, 15 patients in Group II underwent PDT (50J/cm2-600mW/cm2-83sec) and intravitreal pegaptanib combination while, 15 patients in Group III underwent intravitreal pegaptanib monotherapy. Complete ophthalmologic examinations were performed in pre and post treatment visits, and the results were statistically analised. A clinical activity score (CAS) was calculated by using changes in lesion size, amount of hemorrhage, staining pattern in FA and OCT measurement of intra/subretinal fluid. ≤ 3 logMAR lines of decrease in BCVA and decrease in CAS were considered as successful treatment. RESULTS: The mean age of 19 female (42.2%) and 26 male (57.8%) patients was 72.82±8.02 years. Mean follow-up was 13.93±5.87 months. Lesion type was occult in 28 eyes (62.2%). Treatment success rates according to BCVA assessments were 86.7%, 80%, 60% and mean BCVA decrease were 0.3, 1.0, 2.2 logMAR lines in Group I, II and III, respectively (P>0.05). According to the changes in central macular thickness and CAS, no difference was found among the study groups (P=0.850 and P=0.811, respectively). Patients treated with combination regimens had lower intravitreal injection frequencies (P=0.015). CONCLUSION: Combination regimen with intravitreal pegaptanib and low-fluence PDT seems to be safe and effective in stabilizing the clinical activity and BCVA in exudative AMD.     

Pharmacologic management of neovascular age-related macular degeneration: systematic review of economic evidence and primary economic evaluation

Objective: To examine the economic implications for the Canadian health system of pharmacologic treatment of neovascular age-related macular degeneration (AMD).Design: Systematic review of economic literature and a primary economic evaluation.Participants: Economic literature search identified 392 potentially relevant articles, 12 of which were included forfinal review.Methods: Studies were included if they met the following criteria: (i) provision of a summary measure of the trade-off between costs and consequences; (ii) participants of 40 years and older with neovascular AMD; (iii) interventions and comparators: comparison of photodynamic therapy using verteporfin (V-PDT), pegaptanib, bevacizumab, ranibizumab, anecortave acetate, intravitreal triamcinolone, placebo, or clinically relevant combinations; and (iv) outcome reported as an incremental measure of the implication of moving from the comparator to the intervention. The following databases were searched through the OVID interface: MEDLINE, EMBASE, BIOSIS Previews, CINAHL, PubMed, Health Economic Evaluations Database (HEED), and the Cochrane Library. For the economic evaluation, we took a decision analytic approach and modeled a cost-utility analysis, conducting it as a microsimulation of a Markov model.Results: In general, V-PDT is more cost effective than conventional macular laser, and pegaptanib is likely more cost effective than V-PDT. The primary economic analysis revealed ranibizumab to be effective but at an unacceptably high cost per quality-adjusted life year (QALY) (>$50000 per QALY).Conclusion: Although ranibizumab is effective for wet AMD, its cost is unacceptably high based on cost-utility theory.     

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.     

VEGF gene polymorphism and response to intravitreal bevacizumab and triple therapy in age-related macular degeneration

Purpose

To investigate the association between the vascular endothelial growth factor (VEGF) gene and response to either intravitreal bevacizumab (IVB) or photodynamic therapy with intravitreal triamcinolone acetonide and IVB (triple therapy) for neovascular age-related macular degeneration (AMD).

Methods

The study consisted of 94 patients with neovascular AMD who underwent IVB and 79 patients with neovascular AMD who underwent triple therapy. Genotypes were determined for four selected tagging single-nucleotide polymorphism (SNP)s of the VEGF gene.

Results

Of the four SNPs studied, one SNP (rs699946) was associated significantly with visual acuity (VA) changes 12 months after treatment??irrespective of whether they received IVB alone (P = 0.044) or triple therapy 0.010). Baseline VA was not significantly different among the three genotypes of rs699946 in either treatment group. There were no significant differences in the number of treatments, incidence of recurrence, or the period until the recurrence according to VEGF rs699946 genetic variant.

Conclusions

The VEGF gene SNP rs699946 was associated with response to IVB alone and to triple therapy in this study. The G allele in SNP rs699946 can thus be applied as a marker for better visual prognosis in patients with neovascular AMD who receive either IVB or triple therapy.