THE LATEST PUBLISHED RESEARCH

Visual Acuity in Branch Retinal Artery Occlusion
To investigate systematically the natural history of visual outcome in branch retinal artery occlusion (BRAO), the authors of this cohort study included 199 consecutive untreated patients (212 eyes) with BRAO, first seen in their clinic 1973-2000.

According to the authors, all patients had a detailed ophthalmic and medical history at the first visit, as well as a comprehensive ophthalmic evaluation. They performed visual evaluation by recording visual acuity, using the Snellen visual acuity chart and visual fields with a Goldmann perimeter. They performed the same ophthalmic evaluation at each follow-up visit.

Main outcome measures for this study were visual acuity and visual fields. The study authors classified BRAO into permanent (133 eyes) and transient (18 eyes) and cilioretinal artery occlusion (CLRAO; 61 eyes). In eyes with permanent BRAO, of the 61 eyes seen within 7 days of onset, initial visual acuity was ≥20/40 in 74%, central scotoma in 20%, central inferior altitudinal defect in 13% and inferior nasal and superior sector defects in 29% and 24%, respectively. Of those with follow up, in the eyes with visual acuity <20/40, it improved in 79% (11/14), abnormal central visual field defect improved in 47% and abnormal peripheral visual field defect improved in 52%. Of the 18 eyes with transient BRAO, the authors reported that initially 17 (94%) had visual acuity of ≥20/40 and 1 (6%) <20/40, which improved to 20/30 on follow up. Of the 11 eyes with nonarteritic CLRAO alone, visual acuity was <20/40 in 3 eyes, which improved to ≥20/40 in all during follow up. In CLRAO on follow up of 9 eyes, the central field improved in 4. Moreover, when CLRAO was associated with retinal vein occlusion (38 eyes) or giant cell arteritis (12 eyes), visual findings were influenced by the associated diseases.

The authors of this study concluded that these findings show a visual acuity of ≥20/40 is seen initially in 74% of cases of permanent BRAO, 94% of transient BRAO and 73% of nonarteritic CLRAO alone. Additionally, on follow up, in 89%, 100% and 100% of cases, respectively. They believe that the effectiveness of various treatment modalities for visual outcome has to be judged against this background.

Source: Hayreh SS, Podhajsky P, Zimmerman MB. Branch retinal artery occlusion: natural history of visual outcome. Ophthalmol 2009;116(6):1188-1194.e4.

Intravitreal Ranibizumab for Subfoveal CNV Related to AMD
In this Swiss interventional case series, the authors aimed at demonstrating not only prevention of vision loss, but also improvement in best-corrected visual acuity (BCVA) after treatment with ranibizumab on a variable-dosing regimen over 24 months in patients with AMD.

They treated 138 eyes of 138 patients intravitreally with 0.5 mg ranibizumab. Age above 50 years, BCVA 0.2 to 1.2 logarithm of the minimal angle of resolution (logMAR), primary or recurrent subfoveal choroidal neovascularization (CNV) secondary to AMD. They conducted observation procedures after single initial treatment as well as a monthly follow-up exam. Retreatment occurred in case of one of the following: sign of subretinal fluid or intraretinal edema, increase in central retinal thickness (CRT) on optical coherence tomography (OCT), active CNV on fluorescein angiography, increase of metamorphopsia and loss of BCVA >5 letters on Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Main outcome measures, compared with baseline, were proportion of eyes gaining ≥15 letters, proportion of eyes losing or gaining <15 letters and change in CRT.

After 24 months, the mean change in best-corrected visual acuity was +6.3 letters. The authors reported that 30% of eyes gained ≥15 letters. Mean CRT of 386 ± 145 µm at baseline was significantly reduced to 211 ± 39 µm after 24 months (p=.036). Furthermore, mean injection number per patient was 5.6 ± 2.9 and 4.3 from baseline to month 12 and month 12 to 24, respectively.

Intravitreal ranibizumab on a variable-dosing regimen was found to be effective in significantly increasing mean BCVA and reducing CRT. The authors found that this beneficial outcome was achieved with a low-rate of mild ocular adverse effects among their patients.

Source: Rothenbuehler SP, Waeber D, Brinkmann CK, et al. Effects of ranibizumab in patients with subfoveal choroidal neovascularization attributable to age-related macular degeneration. Am J Ophthalmol 2009;147(5):831-837.

Role of CCR3 in Diagnosing and Treating AMD
The researchers in this study found that eosinophil/mast cell chemokine receptor CCR3 targeting might reduce vision loss due to AMD through early detection and therapeutic angioinhibition. They demonstrated that CCR3 is specifically expressed in choroidal neovascular endothelial cells in humans with AMD, and that despite the expression of its ligands eotaxin-1, -2 and -3, neither eosinophils nor mast cells are present in human choroidal neovascularisation (CNV).

Genetic or pharmacological targeting of CCR3 or eotaxins inhibited injury-induced CNV in mice. Furthermore, CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation because it occurred in mice lacking eosinophils or mast cells, and was independent of macrophage and neutrophil recruitment. According to the researchers, CCR3 blockade was more effective at reducing CNV than vascular endothelial growth factor A (VEGF-A) neutralization, which is in clinical use at present, and, unlike VEGF-A blockade, is not toxic to the mouse retina. They also found that in vivo imaging with CCR3-targeting quantum dots located spontaneous CNV invisible to standard fluorescein angiography in mice before retinal invasion.

Source: Takeda A, Baffi JZ, Kleinman ME, et al. CCR3 is a target for age-related macular degeneration diagnosis and therapy. Nature 2009; Jun 14 [Epub ahead of print]. DOI: 10.1038/nature08151.

Retreatment with Ranibizumab and Neurosensory Retinal Volume in Neovascular AMD
Investigators collected data from 50 consecutive patients receiving ranibizumab therapy for neovascular age-related macular degeneration (AMD) to determine the characteristics of patients with AMD who show initial anatomic improvements on optical coherence tomography (OCT) in response to treatment with ranibizumab, but who subsequently regress toward their anatomic baseline.

They analyzed raw Stratus OCT images using custom software (“OCTOR”) and calculated changes in volume of neurosensory retina at months 1, 3 and 6. They also compared baseline demographic and morphologic characteristics.

A total of 42 patients (84%) showed a reduction in total retinal volume 1 month after initial treatment with ranibizumab and of the patients that initially showed a reduction, 16 (38%) maintained this reduction through month 6, whereas 26 patients (62%) demonstrated a subsequent increase in retinal volume. Also, according to the investigators, patients who maintained a reduction in edema received 3.75 ± 1.18 injections of ranibizumab versus 2.96 ± 1.34 injections for patients who did not (p=0.049). Moreover, regression of initial anatomic improvements was associated with worsening of visual acuity (r=0.599, p=0.002).

Patients receiving fewer injections of ranibizumab appeared less likely to maintain anatomic improvements achieved following commencement of ranibizumab therapy, the investigators reported. They associated regression of these improvements with deterioration in visual acuity.

Source: Keane PA, Chang KT, Liakopoulos S, et al. Effect of ranibizumab retreatment frequency on neurosensory retinal volume in neovascular AMD. Retina 2009;29(5):592-600.

Effects of Same-Day, Triple Therapy for Neovascular AMD
The purpose of this retrospective case series was to report the results of same-day triple therapy with reduced fluence photodynamic therapy (PDT), intravitreal dexamethasone and bevacizumab in patients with neovascular age-related macular degeneration (AMD).

The authors reviewed the records of patients who received same-day triple therapy with reduced fluence PDT (25 J/cm²), intravitreal dexamethasone (200 [mu]g) and intravitreal bevacizumab (1.25 mg). They recorded Snellen visual acuity (VA), central macular thickness on optical coherence tomography, IOP and endophthalmitis occurrence. All patients (n = 31) had neovascular subfoveal AMD with at least 1 year of follow up.

The patients were observed for a mean of 13.7 months and mean baseline VA in all patients was 20/80 and vision at final follow up was 20/60 (p=0.69). In patients who received previous treatment for exudative AMD (n = 18), mean baseline VA was 20/100 and vision at final follow up (mean, 13.7 months) was 20/100 (p=0.31). In treatment-naive patients (n = 13), the authors found that mean baseline VA was 20/60 and vision at final follow up (mean, 13.5 months) was 20/40 (p=0.31). In all patients, mean central macular thickness was 293 µm at baseline and 245 µm at final follow up (p=0.053). In previously treated patients (n = 18), mean central macular thickness was 325 µm at baseline and 265 µm at final follow up (p=0.10). According to the authors, in treatment-naive patients, mean central macular thickness was 249 µm at baseline (n = 13) and 218 µm at final follow up (p=0.34). They found that previously treated patients required more antivascular endothelial growth factor injections (mean = 3.6) than treatment-naive patients (mean = 0.8), but that the mean number of repeat triple therapy treatments was 0.3 in both groups. They observed no changes in IOP and endophthalmitis during follow up.

The study authors concluded that same-day triple therapy maintained VA and decreased macular thickness in patients with and without previous antivascular endothelial growth factor therapy. Also, triple therapy may reduce the number of antivascular endothelial growth factor injections in some patients and stabilize vision in some patients not responding to antivascular endothelial growth factor therapy.

Source: Bakri SJ, Couch SM, McCannel CA, Edwards AO. Same-day triple therapy with photodynamic therapy, intravitreal dexamethasone, and bevacizumab in wet age-related macular degeneration. Retina 2009;29(5):573-578.

IVB Dose Comparison for Diffuse Diabetic Macular Edema
In this interventional, retrospective multicenter study, the authors reviewed the clinical records of 82 consecutive patients (101 eyes) with diffuse diabetic macular edema (DDME) to report the 12-month anatomic and ETRS best-corrected visual acuity (BCVA) response after primary intravitreal bevacizumab (IVB, Avastin, 1.25 mg or 2.5 mg) in patients with DDME. They also compared the two different doses of IVB.

All patients with a minimum follow up of 12 months (mean 57.6 ± 8.4 weeks) were included in this analysis and patients underwent ETDRS BCVA testing, ophthalmoscopic examination, optical coherence tomography (OCT) and fluorescein angiography (FA) at baseline and follow up visits.

The mean age of patients was 59.7 ± 9.3 years and the mean number of IVB injections per eye was three (range: one to six injections) at a mean interval of 14.1 ± 10.5 weeks. According to the authors, in the 1.25 mg group at 1 month, BCVA improved from 20/190, logMAR = 0.97 to 20/85, logMAR 0.62 (a difference that was statistically significant [p=0.0001]). They reported that this improvement was maintained throughout the 3-, 6- and 12-month follow up. The mean final BCVA at 12 months was 20/76, logMAR=0.58 (p<0.001), a statistically significant difference from baseline BCVA. They observed similar BCVA changes in the 2.5 mg group. The mean central macular thickness (CMT) in the 1.25 mg group decreased from 419.1 ± 201.1 µm at baseline to 295.11 ± 91.5 µm at 1 month, 302.1 ± 124.2 µm at 3 months, 313.4.1 ± 96.3 µm at 6 months and 268.2 ± 95.5 µm at 12 months (p<0.0001). Similar CMT changes were also observed in the 2.5 mg group. Adverse events included transient high blood pressure in one patient (1.2%), transient increased IOP in one eye (1%) and tractional retinal detachment in one eye (1%). Similar CMT changes were observed in the 2.5 mg group. Adverse events included transient high blood pressure in one patient (1.2%), transient increased intraocular pressure in one eye (1%), and tractional retinal detachment in one eye (1%).

According to the authors, primary IVB at doses of 1.25 to 2.5 mg seem to provide stability or improvement in BCVA, OCT and FA in DDME at 12 months. No difference was observed in their results between IVB at doses of 1.25 mg or 2.5 mg and additionally, their results suggest the need for at least three injections a year to maintain the BCVA results.

Source: Arevalo JF, Sanchez JG, Fromow-Guerra J, et al.; for the Pan-American Collaborative Retina Study Group (PACORES). Comparison of two doses of primary intravitreal bevacizumab (Avastin) for diffuse diabetic macular edema: results from the Pan-American Collaborative Retina Study Group (PACORES) at 12-month follow-up. Graefes Arch Clin Exp Ophthalmol 2009;247(6):735-743.

Foveal Photoreceptor Status and Visual Acuity Following Pars Plan Vitrectomy for Diabetic Macular Edema
To evaluate the correlation between photoreceptor layer status following resolution of diabetic macular edema (DME) by pars plana vitrectomy (PPV) and final visual acuity (VA), investigators in Japan retrospectively studied a series of 69 eyes from 58 patients with DME who were treated for PPV.

They included 37 of the 69 eyes, that were examined by optical coherence tomography (OCT) for at least 6 months and that showed a final macular thickness of <250µm in the study and they assessed the integrity of the photoreceptor inner and outer segments (IS/OS) line in the fovea using OCT in relation to their VA and other characteristics.

The investigators observed no differences in initial VA or in foveal thickness between eyes with or without complete IS/OS at final observation, yet final VA without complete IS/OS was significantly poorer (p=0.004). They noted that VA had improved by more than 2 lines in eight of 10 eyes with complete IS/OS and in 10 of 27 eyes without complete IS/OS. The groups differed significantly with regard to this percentage (p=0.03).

After examining the relationship between the appearance of IS/OS line on OCT images and visual acuity after resolution of DME by vitrectomy, the investigators noted that postop VA of eyes with complete IS/OS after resolution of DME was significantly better than that without complete IS/OS, though macular edema was completely resolved in both groups. In light of their findings, they contend that the postop photoreceptor status of the fovea is closely related to the final VA after resolution of DME by PPV.

Source: Sakamoto A, Nishijima K, Kita M, et al. Association between foveal photoreceptor status and visual acuity after resolution of diabetic macular edema by pars plana vitrectomy. Graefes Arch Clin Exp Ophthalmol 2009; May 9 [Epub ahead of print]. DOI: 10.1007/s00417-009-1107-5.

Impact of Intravitreal Triamcinolone Acetonide Injection on Visual Acuity in Refractory DME
This study sought to compare intravitreal triamcinolone acetonide (IVTA) injection versus no treatment or sub-Tenon triamcinolone acetonide (STTA) injection in improving visual acuity (VA) of patients with refractory diabetic macular edema (DME; unresponsive to focal laser therapy). Databases searched for the study include Medline (1950-September Week 2 2008), The Cochrane Library (Issue 3, 2008) and the TRIP Database (up to September 1, 2008) using no language or other limits.

Randomized controlled trials that consisted of patients with refractory DME, those comparing IVTA injection with no treatment or STTA injection, those reporting VA outcomes and those having a minimum follow-up of 3 months were included.

IVTA injection demonstrated greater improvement in VA at 3 months in the four randomized clinical trials comparing IVTA injection with placebo or no treatment, but the benefit was no longer significant at 6 months. Also, those who received IVTA injection had significantly higher IOP at 3 months and at 6 months and in the two randomized clinical trials comparing IVTA injection with STTA injection, IVTA injection demonstrated greater improvement in VA at 3 months, but not at 6 months. Furthermore, IVTA injection demonstrated no difference in IOP at 3 months or at 6 months.

It was concluded that IVTA injection is effective in improving VA in patients with refractory DME in the short term, but the benefits do not seem to persist in the long term.

Source: Yilmaz T, Weaver CD, Gallagher MJ, et al. Intravitreal triamcinolone acetonide injection for treatment of refractory diabetic macular edema: a systematic review. Ophthalmol 2009;116(5):902-913.

Randomized Comparison of DME Treatments
The results of intravitreal bevacizumab (IVB) injection alone or in combination with intravitreal triamcinolone acetonide (IVT) versus macular laser photocoagulation (MPC) were compared as a primary treatment of diabetic macular edema (DME) in this randomized, 3-arm clinical trial.

A total of 150 eyes of 129 patients with clinically significant DME and no previous treatment were randomly assigned to 1 of the 3 study arms: the IVB group, patients who received 1.25 mg IVB (50 eyes); the IVB/IVT group, patients who received 1.25 mg of IVB and 2 mg of IVT (50 eyes); and the MPC group, patients who underwent focal or modified grid laser (50 eyes). Retreatment was performed at 12-week intervals whenever indicated and the main outcome measure was the change in best-corrected visual acuity (VA) at week 24.

It was noted that VA changes among the groups were statistically significant at 6 (p<0.001) and 24 (p=0.012) weeks and the significant treatment effect was demonstrated in the IVB group at all follow-up visits and in the IVB/IVT group at 6 and 12 weeks. Also, VA changes ± standard deviation at 36 weeks were -0.28 ± 0.25, -0.04 ± 0.33 and +0.01 ± 0.27 logarithm of minimum angle of resolution in the IVB, IVB/IVT and MPC groups, respectively (p=0.053). Furthermore, significant central macular thickness (CMT) reduction was observed in all groups only up to 6 weeks; however, CMT changes were not significant among the groups in all visits. Overall, retreatment was required for 27 eyes up to 36 weeks (14 in the IVB group, 10 in the IVB/IVT group and 3 in the MPC group). In the IVB group, in which a greater VA improvement was observed, only 1 injection was required in 72% of the cases. VA improvement >2 Snellen lines at 36 weeks was detected in 37%, 25% and 14.8% of patients in the IVB, IVB/IVT and MPC groups, respectively.

It was determined that IVB injection in patients with DME yielded a better visual outcome at 24 weeks compared with macular photocoagulation and a change in CMT beyond the 6-week time point that corresponded to the vision change was not detected. No adjunctive effect of IVT was demonstrated.

Source: Soheillian M, Ramezani A, Obudi A, et al. Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema. Ophthalmol 2009;116(6):1142-1150.

PDT for Central Serous Chorioretinopathy
To investigate the effects and prognostic factors related to photodynamic therapy (PDT) for central serous chorioretinopathy (CSC), Korean researchers performed retrospective medical record reviewing of consecutive CSC patients (chronic or persistent typical CSC) treated with conventional PDT (full-dose verteporfin, laser [689 nm] delivery for 83 s, total light energy of 50 J/cm²).

They evaluated overall anatomic and functional outcomes as well as the prognostic influences of various baseline factors (sex, age, duration of symptoms, presence of focal leak and pigment epithelial detachment [PED], SRF size, confluent retinal pigment epithelium (RPE) atrophy, PDT spot size), disintegrity of the junction between foveal outer and inner photoreceptor layer (OS-IS) after resolution and post-treatment RPE changes on outcomes.

Included in this study were 40 patients (41 eyes). According to researchers, anatomic success, defined as complete resolution of serous fluid on optical coherence tomography performed 4-6 weeks after PDT, was achieved in 87.8% of eyes and visual acuity improved significantly (0.19 ± 0.24 lines). Moreover, visual acuity had improved more than one line in 46.3% of the patients and decreased more than one line in 14.6% of patients at the 1-month follow-up visit. The researchers also determined that prolonged symptoms duration (>9 months), PED, confluent RPE atrophy, foveal OS-IS disintegrity and post-PDT RPE changes were associated significantly with visual loss of more than three lines and foveal atrophy. Also, central macular thickness was significantly reduced in patients treated with PDT compared to those treated with focal laser.

PDT for CSC was effective with regard to anatomic and functional outcomes, but visual improvement may be limited in patients with prolonged symptom duration, baseline confluent RPE atrophy, foveal OS-IS disintegrity or progression of RPE atrophy after PDT. The researchers advise that the risk of PDT-induced foveal injury be considered.

Source: Moon JW, Yu HG, Kim TW, et al. Prognostic factors related to photodynamic therapy for central serous chorioretinopathy. Graefes Arch Clin Exp Ophthalmol 2009;May 7 [Epub ahead of print]. DOI : 10.1007/s00417-009-1104-8.