THE LATEST PUBLISHED RESEARCH

Ranibizumab vs. Verteporfin PDT in Patients with AMD
This 2-year, multicenter, international, randomized, double-masked, active-treatment-controlled, phase III clinical trial, designated Anti-vascular endothelial growth factor (VEGF) Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization (CNV) in Age-related Macular Degeneration (ANCHOR), compared ranibizumab with verteporfin photodynamic therapy (PDT) in treating predominantly classic CNV. Patients with predominantly classic, subfoveal CNV not previously treated with PDT or antiangiogenic drugs were randomized 1:1:1 to verteporfin PDT plus monthly sham intraocular injection or to sham verteporfin PDT plus monthly intravitreal ranibizumab (0.3 mg or 0.5 mg) injection. Researchers evaluated the need for PDT (active or sham) retreatment every 3 months using fluorescein angiography (FA).

The primary, intent-to-treat efficacy analysis was at 12 months, with continued measurements to month 24. Key measures included the percentage losing <15 letters from baseline visual acuity (VA) score (month 12 primary efficacy outcome measure), percentage gaining >/= 15 letters from baseline, and mean change over time in VA score and FA-assessed lesion characteristics. The researchers also measured adverse events.

Out of the 423 patients (143 PDT and 140 in each of the two ranibizumab groups), the majority (>/= 77% in each group) completed the study. At month 24, the VA benefit from ranibizumab was statistically significant (p<0.0001 vs. PDT) and clinically meaningful: 89.9% to 90.0% of ranibizumab-treated patients had lost <15 letters from baseline (vs. 65.7% of PDT patients); 34% to 41.0% had gained >/= 15 letters (vs. 6.3% of PDT group), and, on average, VA was improved from baseline by 8.1 to 10.7 letters (vs. a mean decline of 9.8 letters in PDT group). These results were consistent with those from month 12 and changes in lesion anatomic characteristics on FA also favored ranibizumab (all comparisons p<0.001 vs. PDT). Overall, the researchers reported no imbalance among groups in rates of serious ocular and nonocular adverse events. In the pooled ranibizumab groups, 3 of 277 (1.1%) patients developed presumed endophthalmitis in the study eye (rate per injection = 3/5921 [0.05%]).

According to the researchers, ranibizumab provided greater clinical benefit than verteporfin PDT in patients with age-related macular degeneration with new-onset, predominantly classic CNV. Rates of serious adverse events were low.

Source: Brown DM, Michels M, Kaiser PK, et al. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study. Ophthalmol 2009;116(1):57-65.e5.

OCT for Imaging Exudative Macular Diseases
Fourteen eyes of 13 participants were prospectively enrolled in this Japanese study that evaluated the clinical significance of the newly developed long-wavelength probe optical coherence tomography (LP-OCT) for the diagnosis of exudative macular diseases.

Seven type I and five type II choroidal neovascularization (CNV) cases were associated with age-related macular degeneration (AMD) and idiopathic neovascularization and one case of polypoidal choroidal vasculopathy (PCV). For the purposes of the study, a custom-built LP-OCT based on swept-source OCT (SS-OCT) technology was used. It employs a probe beam with a wavelength of 1060 nm that provides deeper penetration into the choroid and higher image contrast to the structures beneath the retinal pigment epithelium (RPE) and pathologic tissues than does conventional OCT. The depth resolution is 10.4 µm in tissue and the measurement speed is 28,000 depth scans/s. All the eyes were also examined by standard short wavelength probe OCT (SP-OCT). The image contrasts of the LP- and SP-OCT were qualitatively evaluated and analyzed by Wilcoxon’s paired and signed rank test and Spearman's rank correlation test.

High-contrast visualization of the diseases beneath the RPE, CNV or fibrin was attained in 10 of 14 eyes and these diseases were almost invisible in the SP-OCT images. Additionally, the LP-OCT of the remaining eyes revealed significant improvement in the image contrast beneath the RPE and CNV, and qualitative evaluation of the image contrast and subsequent statistical test indicated statistically significant improvement in the image penetration to the choroid of LP-OCT.

It was determined that LP-OCT provided significant improvement in the image contrast of exudative macular diseases.

Source: Yasuno Y, Miura M, Kawana K, et al. Visualization of sub-retinal pigment epithelium morphologies of exudative macular diseases by high-penetration optical coherence tomography. Invest Ophthalmol Vis Sci 2009;50:405-413.

Effect of Intravitreal Bevacizumab on Treatment-Naïve AMD Patients
In this prospective, uncontrolled, pilot study of 26 eyes of 26 patients, investigators treated all eyes previously treatment-naïve to photodynamic therapy (PDT), argon laser or anti-vascular endothelial growth factor (VEGF) with one or more intravitreal injections of 1.25 mg bevacizumab to report the effects of the drug in treatment-naïve patients with exudative age-related macular degeneration (AMD) assessed by visual acuity (VA), optical coherence tomography (OCT) and contrast sensitivity.

They noted that of the 26 patients, 15 (57.7% had occult choroidal neovascularization (CNV), 6 (23.1%) had predominantly classic CNV and 5 (19.2%) had minimally classic CNV. Ophthalmic outcome measures included changes in standardized Early Treatment Diabetic Research Study (ETDRS) VA, contrast sensitivity and OCT. The investigators examined all patients at baseline and 1 week, 6 weeks, 3 months and 6 months after the first injection. Re-treatment was given on an "as-needed" basis. Two patients chose to discontinue the study, so 24 eyes of 24 patients completed 6 months of follow up.

Mean ETDRS VA score improved from 55 letters at baseline to 60 letters at 1 week (p<0.01) and to 61 letters at 6 weeks (p<0.01). The investigators noted no significant improvement in VA from baseline after 3 and 6 months and patients with pigment epithelial detachment (PED) had a significantly worse outcome in VA at 6 months. Contrast sensitivity improved from baseline to 3 or 6 months, but this improvement was not statistically significant. Also, mean macular thickness decreased significantly from baseline to all follow-up examinations (p<0.01).

These results indicate that 1.25 mg intravitreal bevacizumab is associated with functional as well as morphological improvement among treatment-naïve AMD patients.

Source: Pedersen KB, Sjolie AK, Moller F. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration in treatment-naïve patients. Acta Ophthalmol 2009;Dec. 16 [Epub ahead of print].

Promising Results with Intravitreal Bevacizumab for Myopic CNV
To evaluate the short-term efficacy and safety of intravitreal bevacizumab for the treatment of myopic choroidal neovascularization (CNV) secondary to pathologic myopia, 20 eyes from 20 patients with myopic CNV participated in this prospective, nonrandomized, interventional case series.

All patients were scheduled for three monthly intravitreal bevacizumab 1.25 mg injections and Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), foveal center thickness (FCT) on optical coherence tomography (OCT) and fluorescein angiographic findings were examined both before and after treatment.

Patients were followed for 12 months. The mean BCVA (± SD) improved significantly (p=.000001) to 43 (± 12.38) letters (Snellen equivalent: 20/35). At 12-month follow up, BCVA improved 10 letters or more in 18 (90%) out of 20 treated eyes and improved 15 letters or more in 14 (70%) out of 20 treated eyes. No treated eyes experienced a worsening of BCVA from baseline and the mean FCT (± SD) at baseline was 223 (± 47.43) µm. At 12 months after treatment, the mean FCT (± SD) reduced to 206 (± 50.87) µm. This reduction in FCT after treatment was not statistically significant (p=.11). At 12 months follow up, absence of fluorescein leakage from the CNV was demonstrated in 19 (95%) out of 20 treated eyes and persistent leakage in one eye (5%). None of the 19 eyes that had CNV closure experienced recurrence at 12-month follow up and no ocular or systemic adverse effects from treatment were encountered.

Although no apparent short-term safety concerns were associated with these results, further studies will be needed to better determine long-term efficacy and safety. At 12 months, treated eyes had a significant improvement in visual acuity. OCT findings, as well, showed a trend consistent with the beneficial changes observed for visual acuity. Treatment also resulted in complete absence of angiographic leakage in 95% of eyes.

Source: Gharbiya M, Allievi F, Mazzeo L, Gabrieli CB. Intravitreal bevacizumab treatment for choroidal neovascularization in pathologic myopia: 12-month results. Am J Ophthalmol 2009;147:84-93.

Intravitreal Bevacizumab for Myopic CNV After 1 Year
A total of 63 eyes of 63 patients were treated with intravitreal bevacizumab (IVB) for choroidal neovascularization attributable to pathological myopia (mCNV) in this retrospective case series. According to the authors, 1 mg of bevacizumab was injected into the vitreous via the pars plana. IVB was repeated after two to three months if there was fluorescein leakage in fluorescein in fluorescein angiogram (FA), apparent subretinal fluid in optical coherence tomography (OCT) persisted, or both. Main outcome measures were best-corrected visual acuity (BCVA) and CNV size measured on FA.

IVB was performed one to six times during the first 12 months (mean, 2.4 ± 1.4 times). The size of the mCNV decreased and the BCVA improved significantly (p < .01 for both comparisons). The BCVA improved more than three lines in 25 eyes (40%), worsened more than three liens in three eyes (5%) and was unchanged in 35 (56%) eyes 12 months after. It was reported that fluorescein leakage from the mCNV ceased in 30 eyes (48%), diminished in 28 (44%) and was unchanged in five (8%) eyes. Stepwise analysis showed that the number of IVB (p<.01), macular atrophy (p<.05) and myopic atrophy (p<.05) were significant predictive factors for BCVA at 12 months.

The study authors concluded that although their study lacked a control group, IVB seems to be an effective treatment for mCNV after a long term and the absence of chorioretinal atrophy and that of recurrence and persistency of mCNV are positive predictive factors.

Source: Ikuno Y, Sayanagi K, Soga K, et al. Intravitreal bevacizumab for choroidal neovascularization attributable to pathological myopia: one-year results. Am J Ophthalmol 2009;147:94-100.

Treatment Success of Bevacizumab and Ranibizumab for CNV in Multifocal Choroiditis
Researchers described the treatment of multifocal choroiditis (MFC)-associated choroidal neovascularization (CNV) with intravitreal bevacizumab and/or ranibizumab in this retrospective, interventional case series. Six eyes of five patients with MFC-associated CNV were treated with intravitreal bevacizumab and/or ranibizumab and main outcome measures were visual acuity at 1, 3 and 6 months after the initial injection.

According to the researchers, bevacizumab and ranibizumab were effective at improving visual acuity over six months in a small series of patients with MFC-associated CNV. Previous therapies (number of eyes treated) included sub-Tenon’s corticosteroids (2), intravitreal corticosteroids (1), photodynamic therapy (1) and thermal laser (1). They reported that the mean number (range) of antivascular endothelial growth factor injections per eye was 2.3 (1-6) and the mean duration (range) of follow up per patient was 41.5 (25-69) weeks. Five of six eyes improved to 20/30 acuity or better at 6 months. One eye suffered a subfoveal rip of the retinal pigment epithelium with 20/400 acuity and there was a qualitative decrease in clinical and angiographic evidence of CNV.

The researchers note that tears of the retinal pigment epithelium may occur after intravitreal antivascular endothelial growth factor therapy in MFC-associated CNV.

Source: Fine HF, Zhitomirsky I, Freund KB, et al. Bevacizumab (Avastin) and ranibizumab (Lucentis) for choroidal neovascularization in multifocal choroiditis. Retina 2009;29:8-12.

Impact of Intravitreal Bevacizumab at the Time of Cataract Surgery on Progression of Diabetic Retinopathy and Diabetic Maculopathy
A total of 68 eyes (68 patients) with diabetic retinopathy (DR) and cataract were recruited for this prospective study that evaluated the role of intravitreal bevacizumab, injected at the time of cataract surgery, on the postop progression of DR and diabetic maculopathy (DM).

Patients were randomized to a standardized procedure of phacoemulsification with IOL implantation alone (control group) or to receive 1.25 mg intravitreal bevacizumab at the end of surgery (intervention group). Both DR and DM were assessed at each postop visit during a 6-month follow up and the intravitreal administration of 1.25 mg bevacizumab at the time of cataract surgery was found to be safe and effective in preventing the progression of DR and DM in patients with cataract and DR.

Progression of DR occurred in 15 (45.45%) of 33 eyes in the control group and 4 (11.42%) of 35 eyes in the intervention group (p=.002), while progression of DM occurred in 17 eyes (51.51%) in the control group and 2 eyes (5.71%) in the intervention group (p=.0001). No statistically significant difference in postoperative visual acuity between the two groups was observed (p=.772) and two eyes in the control group and none in the intervention group progressed to neovascular glaucoma. Finally, the mean postop central macular thickness and mean macular thickness were not statistically significantly different between the two groups (p=.874 and .942, respectively).

Source: Cheema RA, Al-Mubarak MM, Amin YA, Cheema MA.Role of combined cataract surgery and intravitreal bevacizumab injection in preventing progression of diabetic retinopathy : prospective randomized study. J Cataract Refract Surg 2009;35(1):18-25.

Vitreous Fluid Levels in Macular Edema with Central Retinal Vein Occlusion
This retrospective case-control study investigated whether interleukin (IL-6) or vascular endothelial growth factor (VEGF) influences macular edema in patients with central retinal vein occlusion (CRVO).

Retinal ischemia was evaluated by measuring the area of capillary nonperfusion using fluorescein angiography and the public domain Scion Image program and macular edema was examined by optical coherence tomography in 27 patients who had macular edema with CRVO and 16 patients with nonischemic ocular diseases (control group). Additionally, vitreous fluid samples were obtained at pars plana vitrectromy and VEGF and IL-6 levels in vitreous fluid and plasma were determined with enzyme-linked immunosorbent assay kits. Main outcome measures were vitreous fluid levels of IL-6 and VEGF.

The vitreous fluid levels of VEGF (median: 435 pg/ml) and IL-6 (median: 41.2 pg/ml) were significantly higher in the patients with CRVO than in the control group (median: 62.4 pg/ml and 1.07 pg/ml, respectively, p=0.0046 and p<0.0001, respectively). The vitreous fluid level of VEGF was significantly correlated with that of IL-6 (p=0.0029) and vitreous fluid levels of both VEGF and IL-6 were significantly higher in patients with CRVO who had retinal ischemia than in those without ischemia (p<0.0001 and p=0.0003, respectively). Vitreous fluid levels of VEGF and IL-6 were also significantly correlated with the severity of macular edema (p=0.0014 and p=0.0047, respectively).

VEGF may increase vascular permeability in patients with macular edema and CRVO, whereas IL-6 may also contribute by acting together with or via VEGF.

Source: Noma H, Funatsu H, Mimura T, et al. Vitreous levels of interleukin-6 and vascular endothelial growth factor in macular edema with central retinal vein occlusion. Ophthalmol 2009;116(1):87-93.

Intravitreal Ranibizumab and VA in CRVO
This prospective, interventional case series evaluated intravitreal injection of ranibizumab as a potential treatment for decreased visual acuity (VA) secondary to central retinal vein occlusion (CRVO) and determined that intravitreal ranibizumab used over a period of one year improved mean VA with low rates of adverse events in patients with CRVO.

Patients with CRVO were administered intravitreal ranibizumab 0.5 mg at baseline and monthly for two additional doses. The patients were given additional ranibizumab if they had macular edema as determined by optical coherence tomography or any new intraretinal hemorrhage and were evaluated for number of required injections, side effects, changes in VA and macular thickness.

At baseline, 20 eyes of 20 patients had a mean age of 72.1 years, a mean VA of 45.8 Early Treatment of Diabetic Retinopathy letters, and a mean central macular thickness of 574.6 µm. Of the 20 eyes, five previously had received intravitreal triamcinolone and 11 had received intravitreal bevacizumab and at 12 months of follow up, the mean VA improved to 64.3 letters and the central macular thickness decreased to 186 µm (both different than baseline values; p<.001) using a mean of 8.5 injections. The change in macular thickness was not correlated with the changes in VA and in one patient with a history of transient ischemic attack, an ischemic stroke developed, but no sequela resulted. Another patient developed vitreomacular traction, but had improved acuity as compared with baseline. No infections, retinal tears or detachments were reported.

Source: Spaide RF, Change LK, Klancnik JM, et al. Prospective study of intravitreal ranibizumab as a treatment for decreased visual acuity secondary to central retinal vein occlusion. Am J Ophthalmol 2009;147:298-306.

Long-Term Effect of Intravitreal Bevacizumab Therapy for Macular Edema Secondary to BRVO
In this prospective, interventional case series, 23 consecutive, previously untreated eyes with perfused macular edema due to branch retinal vein occlusion (BRVO) were treated with intravitreal bevacizumab (1.25 mg) injections and followed for one year to investigate the long-term effectiveness of the drug. Main outcome measures were visual acuity (VA) and central retinal thickness (CRT) and VA data were adapted to the non-logarithmic VA charts used in the previously published grid laser photocoagulation BRVO Study.

Repetitive intravitreal bevacizumab injections resulted in a significant long-term improvement of VA and CRT (the median VA gained 3.0 lines from baseline at 48 weeks and there was a significant decrease of 39% of the median CRT). The number of re-injections necessary to maintain this effect declined over time (the mean number of re-injections was 1.6 during the first 6 months of follow up and only 0.8 during the subsequent 6 months). In 65% of the cases, adapted VA data showed a gain of 1 or more lines and no eye lost more than 1 line. The treatment seems to be only slightly better, however, than grid laser photocoagulation.

Source: Jaissle GB, Leitritz M, Gelisken F, et al. One-year results after intravitreal bevacizumab therapy for macular edema secondary to branch retinal vein occlusion. Graefes Arch Clin Expo Ophthalmol 2009;247:27-33.

Evaluation of Hypoxia Tolerance and RVO
Consecutive patients presenting with retinal vein occlusion (RVO) following exposure to transient hypoxia (Group 1, 8 males) were compared with healthy subjects (Group 2, 8 males) in this pilot study to determine whether a difference in hypoxia tolerance exists between the two groups. The authors performed cardiovascular and plasma tests as well as functional respiratory evaluation at rest and during exercise at both normal oxygen levels (21% O2) and in hypoxia (11.6% O2). They used the Wilcoxon test for statistical analysis.

Both groups had similar mean ages: Group 1, 47.5 years and Group 2, 53 years. Three patients in Group 1 had glucose or lipid abnormalities, one had hypertension and one had minor thalassanemia. As for Group 2, one patient had hypertension. The authors reported that at rest in hypoxia, the oxyhemoglobinic desaturation was significantly different (p=0.03) in Group 1 compared to Group 2 (-13.8 versus -9.3). At exercise in hypoxia, the oxyhemoglobinic desaturation was similar in both groups, but there was a statistically significant increase in both systolic (189 versus 155 mmHg; p=0.01) and diastolic (94 versus 77 mmHg; p=0.03) blood pressure in Group 1. They also reported higher ventilation rate and increased heart rate during hypoxia in Group 1 compared with Group 2. These differences were not statistically significant.

Patients with RVO following exposure to transient hypoxia demonstrated intolerance to hypoxia and were significantly different from healthy subjects in their response to hypoxia. The authors believe that a larger study is required to confirm these preliminary results.

Source: Mauget-Faysse M, Germain-Pastene M. Hypoxia tolerance and retinal vein occlusion : a pilot evaluation. Eur J Ophthalmol 2009;19(1):86-90.

Bevacizumab in Perifoveal Telangiectasia
Researchers at the Bascom Palmer Eye Institute conducted a retrospective review to determine whether inhibition of vascular endothelial growth factor-A affects visual acuity, fluorescein angiographic and optical coherence tomography (OCT) outcomes in patients with perifoveal telangiectasia (PT), also referred to as macular telangiectasia, Type 2. They performed best-corrected visual acuity (BCVA), fluorescein angiography and OCT measurements in the nine eyes of eight patients identified.

Five of the nine eyes had proliferative PT characterized by subretinal neovascularization involving the macula. Follow up after treatment ranged from four to 27 months. The mean BCVA remained stable for the four eyes with nonproliferative PT and in the five eyes with proliferative PT, BCVA was unchanged or improved after treatment. All eyes demonstrated decreased intraretinal leakage no fluorescein angiography after an injection of bevacizumab, and eyes with proliferative PT showed decreased growth and leakage of the subretinal neovascularization. The researchers reported that the mean decrease in OCT central retinal thickness was <30 µm.

They concluded that in nonproliferative PT, intravitreal bevacizumab decreases flurorescein angiographic leakage in PT, but has no short-term effect on visual acuity or OCT appearance. In proliferative PT, however, intravitreal bevacizumab arrests the leakage and growth of subretinal neovascularization with the possibility of visual acuity improvement.

Source: Kovach JL, Rosenfeld PJ. Bevacizumab (Avastin) therapy for idiopathic macular telangiectasia type II. Retina 2009;29:27-32.

Screening for Retinal Tears in Acute Symptomatic Age-Related PVD
The authors of this cross-sectional study with prospective data collection consecutively enrolled 239 patients with acute-onset age-related posterior vitreous detachment (PVD) in a nonreferral hospital to evaluate the performance characteristics of B-scan ultrasonography (US) as a diagnostic test for the detection of retinal tears in acute symptomatic age-related PVD.

The study intended to meet the 14 items proposed by the Quality Assessment of Diagnostic Accuracy Studies panel and the authors performed a comprehensive eye examination including vitreous and retinal biomicroscopy on an emergency basis followed by blind B-scan kinetic US. They also analyzed sensitivity, specificity and predictive values of the index test (B-scan US) and compared them with the standard reference (baseline examination) and in cases of disagreement between both diagnostic methods, they established a new gold standard based on the findings of subsequent directed indirect ophthalmoscopy based on the echographic findings. Lastly, the authors calculated positive and negative likelihood ratios and a likelihood nomogram with pretest and posttest odds of retinal tears for B-scan US and used index test performance for the detection of retinal tears secondary to age-related PVD as main outcome measures.

According to the authors, both diagnostic methods performed comparably and the sensitivity of B-scan US for detection of retinal tears was 96% and that of baseline examination was 89%. Both methods had similar negative predictive values of 99% and B-scan US specificity was 98%. The estimated pretest and posttest probability for a positive B-scan US were 10.8% and 89%, respectively.

B-scan kinetic US is a noninvasive and accurate diagnostic method for the detection of retinal tears that can be reliably used in no view or small pupil cases with symptomatic PVD.

Source: Lorenzo-Carrero J, Perez-Flores I, Cid-Galano M, et al. B-Scan ultrasonography to screen for retinal tears in acute symptomatic age-related posterior vitreous detachment. Ophthalmol 2009 ;118(1) :94-99.