THE LATEST PUBLISHED RESEARCH

Effect of Bevacizumab Therapy on Growth Factor and Cytokine Concentrations in RVO
A prospective clinical trial of 13 eyes of patients with central retinal vein occlusion (CRVO, n=5) or branch retinal vein occlusion (BRVO, n=8) investigated the concentrations of growth factors and inflammatory cytokines in these eyes before and during therapy with bevacizumab and identified associations with disease activity.

Bevacizumab was administered intravitreously at baseline and at months and 2; retreatments were given at monthly visits if optical coherence tomography (OCT) showed edema or when vision loss occurred. Aqueous humor samples were taken each time injections were performed. Follow up was 15 months and samples from patients with cataract served as the control. Moreover, multiplex bead assays were used for measurement of 28 growth factors and cytokines.

Vascular endothelial growth factor (VEGF) levels during therapy with bevacizumab were reduced to below detection in the first 2 months. Whenever criteria for retreatment were met, VEGF was measurable again. The decrease in VEGF was associated with a decrease in central retinal thickness (CRT) and improvement in visual acuity (VA). Also, significantly increased concentrations of VEGF, IL-8, IP-10, MCP-1 and PDGF-AA were observed in aqueous humor samples of patients with CRVO compared with the control samples.

VEGF levels were significantly elevated in patients with CRVO compared with control subjects and intravitreal injections of bevacizumab resulted in a substantial decrease of VEGF under physiologic levels and remained low under the loading dose of three consecutive monthly retreatments. Macular edema was related to VEGF levels in the aqueous humor.

Source: Funk M, Kriechbaum K, Prager F, et al. Intraocular concentrations of growth factors and cytokines in retinal vein occlusion and the effect of therapy with bevacizumab. Invest Ophthalmol Vis Sci 2009; 50:1025-1032.

Intravitreal Bevacizumab's Involvement in Intraoperative Bleeding During Vitrectomy
An institutional study involving 20 consecutive patients with diabetic retinopathy and macula involving tractional retinal detachment (TRD) of recent (3 months) onset compared the amount of intraoperative intraocular bleeding in these patients undergoing pars plana vitrectomy (PPV) with and without preoperative intravitreal bevacizumab (IVB) injection. The patients were randomly assigned to PPV only (PPV group) or PPV combined with one IVB (1.5 mg/0.06 mL) injection 2 weeks prior to surgery (BEV/PPV group) and all of them underwent 23-gauge PPV 3 weeks after baseline. The main outcome measure was erythrocyte count in the fluid retrieved from the vitrectomy cassette using a Neubauer counting chamber.

The mean (standard deviation) erythrocyte count was significantly lower in the BEV/PPV group (14865 x 1000 [±19332 x 1000; median, 4500 x 1000] cells) compared with the PPV group (176240 x 1000 [±108375 x 1000; median, 166600 x 1000] cells), p<0.0001. No major adverse events were identified.

While preoperative IVB injection was associated with reduced intraocular bleeding during the 23-gauge PPV for diabetic macula-involving TRD, further studies are warranted to confirm the study's preliminary findings.

Source: Lucena DR, Ribeiro JAS, Costa RA, et al. Intraoperative bleeding during vitrectomy for diabetic tractional retinal detachment with versus without preoperative intravitreal bevacizumab (IBeTra Study) Br J Ophthalmol 2009; Feb 10 [Epub ahead of print]. DOI:10.1136/bjo.2008.151233.

Surgical Adjunct Treatment for Diabetic Traction Retinal Detachment
In this retrospective, comparative, consecutive, interventional case series, researchers investigated the feasibility and efficacy of microincision vitrectomy surgery (MIVS) combined with intravitreal bevacizumab (IVB) as a surgical adjunct for treating traction retinal detachment (TRD) secondary to severe proliferative diabetic retinopathy (PDR).

A total of 71 eyes of 59 consecutive patients who underwent primary vitrectomy for diabetic TRD were followed for more than 6 months after surgery and researchers compared eyes that received IVB (1 mg) as a preop adjunct followed by MIVS (IVB/MIVS group, 38 eyes [33 patients]) from November 2005 through December 2007 with eyes that underwent conventional 20-gauge pars plana vitrectomy (20-g PPV group, 33 eyes [26 patients]) from September 2003 through October 2005. Primary and ultimate anatomic success, intraoperative and postoperative complications as well as final visual success with at least 6 months of follow up were main outcome measures.

According to the researchers, the primary and ultimate anatomic success rates (95% vs. 91% and 100% in both groups, respectively) and the mean visual acuity changes did not differ significantly between groups; the surgical time and intraoperative bleeding in the IVB/MIVS group decreased significantly compared with the 20-g PPV group (p<0.001). They also noted that the rate of visual improvement of 3 lines or more at the 6-month follow up was 68% in the IVB/MIVS group and 49% in the 20-g PPV group, respectively. Progression of the preexisting TRD after IVB occurred in 7 eyes (18%). Additionally, absence of previous laser photocoagulation (p=0.025) and the presence of a ring-shaped fibrovascular membrane (p=0.013) were relevant findings in eyes with these IVB-induced complications.

What the researchers found is that IVB plus MIVS offers comparable anatomic success compared with conventional 20-g PPV in patients with TRD resulting from severe PDR. This technique shortens the surgical time with fewer intraoperative complications and favorable visual recovery; however, caution should be taken because of rapid progression of the preexisting TRD after IVB in some patients.

Source: Oshima Y, Shima C, Wakabayashi T, et al. Microincision vitrectomy surgery and intravitreal bevacizumab as a surgical adjunct to treat diabetic traction retinal detachment. Ophthalmology 2009; March 9 [Epub ahead of print].

Photoreceptor Inner and Outer Segment Junction and Visual Acuity Following ERM Surgery
Seventy eyes of 70 consecutive patients who had undergone vitrectomy for idiopathic epiretinal membrane (ERM) were examined by optical coherence tomography before surgery as well as 3 and 6 months after surgery in an investigation of the relationship between the presence of the photoreceptor inner and outer segment (IS/OS) junction and visual acuity after ERM surgery.

The IS/OS junction was graded into three grades and the time course of recovery of the IS/OS junction, central foveal thickness (CFT) and best-corrected visual acuity (BCVA) during the postop period was studied.

A normal IS/OS junction was detected in 47.1% of the eyes before surgery, in 65.7% at 3 months and in 75.7% at 6 months after. A significant correlation was noted between the IS/OS grade and BCVA before and at 3 and 6 months after the operation (p=0.0001, p<0.0001, p<0.0001, respectively). Additionally, the preoperative IS/OS junction grade correlated significantly with BCVA at 6 months (p=0.0239). CFT, however, did not correlate significantly with BCVA at 3 and 6 months.

The presence of a normal IS/OS junction was associated with good visual acuity after ERM surgery. A normal IS/OS junction probably indicates morphological and functional recovery of the photoreceptors.

Source: Mitamura Y, Hirano K, Baba T, Yamamoto S. Correlation of visual recovery with presence of photoreceptor inner/outer segment junction in optical coherence images after epiretinal membrane surgery. Br J Ophthalmol 2009;93(2):171-175.

Effect of Sub-Tenon's Injection of Triamcinolone on Vision Loss in Eyes with Diabetic Retinopathy
In evaluating the efficacy of a single posterior sub-Tenon's capsule injection of triamcinolone acetonide (PSTA) before panretinal photocoagulation (PRP), investigators of this 6-month study found that PSTA before PRP appears to be beneficial in preventing PRP-induced visual loss in eyes with severe nonproliferative or proliferative diabetic retinopathy by reducing the change of macular thickening.

The investigators randomized 82 eyes of 41 patients with bilateral severe nonproliferative diabetic retinopathy or proliferative diabetic retinopathy to a single PSTA 20 mg or to no injection before PRP and used change in best-corrected visual acuity (BCVA) at 6 months compared to that at baseline employing logarithm of the minimum angle of resolution (logMAR) as the primary endpoint. Secondary endpoints were changes in retinal thickness and IOP.

They found the mean changes in logMAR BCVA at 6 months compared to that at baseline was a worsening of 0.010 ± 0.029 in the control group (no injection) and an improvement of 0.072 ± 0.028 in the PSTA group, which constituted a significant difference (p=.04). They noted no significant differences between the two groups in IOP at any follow-up point.

Source: Unoki N, Nishijima K, Kita M, et al. Randomized controlled trial of posterior sub-tenon's triamcinolone as adjunct to panretinal photocoagulation for treatment of diabetic retinopathy. Br J Ophthalmol 2009; Feb 12 [Epub ahead of print].

Safety and Efficacy of Panretinal Photocoagulation Plus Intravitreal Bevacizumab in Treating Proliferative Diabetic Retinopathy
The authors of this Korean study evaluated the efficacy and safety of intravitreal bevacizumab as an adjunctive treatment to panretinal photocoagulation (PRP) for high-risk proliferative diabetic retinopathy with or without clinically significant macular edema (CSME) and found that intravitreal bevacizumab before PRP can be an effective adjunctive treatment to PRP in the treatment of high-risk, proliferative diabetic retinopathy, especially if no CSME is present.

They administered intravitreal bevacizumab (1.25 mg/0.05 mL) before PRP (Plus group) or PRP alone (PRP group) in 41 eyes with high-risk proliferative diabetic retinopathy. Primary outcome measures were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT); secondary outcome measures were the proportion of visual loss >/= 0.1 logMAR, increase in CMT >/= 50 mum and eyes with development of vitreous hemorrhage.

The study authors found that BCVA was significantly worse at 3 months (p=0.041) in the PRP group, whereas in the Plus group, there was no significant change. Also that CMT decreased significantly at 1 month and 3 months (p=0.012, 0.008) in the Plus group, whereas in the PRP group, there was no significant change. In eyes with CSME, there was no significant change in BCVA in both groups. CMT decreased significantly at 1 month and 3 months (p=0.003, 0.001) in the Plus group, whereas in the PRP group, there was no significant change. Conversely, in eyes without CSME, BCVA was significantly worse at 1 month and 3 months (p=0.047, 0.011) in the PRP group, whereas in the Plus group, there was no significant change. Furthermore, CMT was significantly worse at 1 month and 3 months (p=0.004, 0.016) in the PRP group, whereas in the Plus group, there was no significant change. Also in eyes without CSME, the proportion of eyes with visual loss >/=0.1 logMAR at 1 month was significantly higher in the PRP group than in the Plus group (p=0.020). The proportion of eyes with development of vitreous hemorrhage was significantly lower in the Plus group than in the PRP group (p=0.023).

Source: Cho WB, Oh SB, Moon JW, Kim HC. Panretinal photocoagulation combined with intravitreal bevacizumab in high-risk proliferative diabetic retinopathy. Retina 2009; Mar 2 [Epub ahead of print].

Role of Diabetes in Retinopathy and the Metabolic Syndrome
A population-based, cross-sectional study from the University of Illinois Eye and Ear Infirmary evaluated the association between the metabolic syndrome and retinopathy in persons 40 years of age and older with gradable fundus photographs in the Third National Health and Nutrition Examination Survey (NHANES III).

Fundus photographs were graded for retinopathy, and clinical and laboratory data were used to define the metabolic syndrome. Logistic regression was performed using the presence of metabolic syndrome or one of the metabolic syndrome components as the independent variable and with the presence of retinopathy as the dependent variable. Main outcome measures were the odds ratio (OR) of retinopathy in persons with the metabolic syndrome, analyzed both for the total NHANES III population (n=8,205) and for those in the nondiabetic population (n=6,582).

As estimated from the NHANES III sample, 5.4% of all persons and 3.5% of nondiabetic persons from the civilian noninstitutionalized United States population 40 years of age and older had retinopathy. The relationship between the metabolic syndrome and retinopathy (OR, 2.23; 95% confidence interval [CI], 1.69 to 2.95) disappeared in analyses stratified by diabetes status. Among the nondiabetic population, there was no association between the metabolic syndrome and retinopathy (OR, 1.23; 95% CI, 0.77 to 1.99), but there was an association between high blood pressure and retinopathy (OR, 1.61; 95% CI, 1.09 to 2.37).

Based on this study's findings, there was no evidence of an association between the metabolic syndrome and retinopathy independent of diabetes status. However, prospective studies are warranted to determine the significance of the metabolic syndrome for predicting risk of ocular and systemic disease independent of diabetes.

Source: Keenan JD, Fan AZ, Klein R. Retinopathy in nondiabetic persons with the metabolic syndrome: findings from the Third National Health and Nutrition Examination Survey. Am J Ophthalmol 2009; Feb. 25 [Epub ahead of print].

Early Treatment of Human Choroidal Neovascularization with Intravitreal Triamcinolone Acetonide
In evaluating the early effects of triamcinolone acetonide (TA) on inflammation, proliferation and vascular endothelial growth factor (VEGF) in human choroidal neovascularization (CNV), researchers conducted a retrospective review of an interventional case series of 29 patients who underwent macular translocation. They found that triamcinolone acetonide has no inhibitory effect on macrophage infiltration or intercellular adhesion molecule-1 (ICAM-1), Thy-1 or VEGF expression in CNV membranes in the early term.

Fourteen CNV membranes without previous therapy (control CNV group) and 4 CNV membranes excised 3 days after photodynamic therapy (PDT CNV group) comprised the control groups. The researchers treated 11 patients with intravitreal TA (TA CNV group; n=5) or PDT and TA combined (PDT + TA CNV group; n=6) 3 to 9 days preop and stained the CNV membranes for cytokeratin 18, CD34, VEGF, ICAM-1, E-selectin, CD68, CD45, Ki-67 and Thy-1.

The researchers found that treatment with TA and PDT + TA resulted in increased immunostaining of ICAM-1 in endothelial cells and the stroma and a higher percentage of Thy-1 expression than controls. The density of macrophages was significantly increased in PDT + TA CNV membranes, while leukocyte density and proliferative activity were lower in TA and PDT + TA CNV membranes. The total VEGF score was significantly increased in TA and PDT + TA CNV membranes compared with the control CNV membranes. Evidence of VEGF in the retinal pigment epithelium of PDT + TA CNV membranes was stronger than in control CNV membranes.

The clinical benefits of TA are probably not based on pure anti-inflammatory or VEGF-suppressing mechanisms.

Source: Tatar O, Adam A, Shinoda K, et al. Early effects of intravitreal triamcinolone acetonoide on inflammation and proliferation in human choroidal neovascularization. Arch Ophthalmol 2009;127(3):275-281.

Cytokine Concentration in Patients with CNV Associated with AMD After Bevacizumab Treatment
Korean investigators evaluated the concentration of various cytokines in the aqueous humor of patients with naïve, recurrent and regressed choroidal neovascularization (CNV) of AMD after bevacizumab treatment.

During cataract surgery, they collected aqueous humor samples from 36 eyes with AMD and 10 controls. Of 36 patients with AMD, 5 eyes were naïve to bevacizumab injection, 14 had recurrent CNV after bevacizumab treatment and 17 eyes had regressed CNV after bevacizumab treatment. Cytokines were measured by an immunoassay using multianalyte biochip array technology and no significant difference in the cytokine levels was noted between the control group and the naïve CNV group (all p>0.05).

Vascular endothelial growth factor (VEGF) in both naïve (66.8 ± 35.1 pg/mL) and recurrent CNV groups (55.7 ± 63.0 pg/mL) was significantly higher compared with regressed CNV group (9.8 ± 12.8 pg/mL, p=0.025 and p=0.004, respectively) but was not statistically different from the control group (81.8 ± 43.7 pg/mL, p=0.310 and p=0.212, respectively). According to the investigators, the aqueous humor level of tumor necrosis factor-alpha and interleukin (IL)-2 was significantly lower in recurrent CNV group (p=0.036 and p=0.019) compared with the control group. In the active CNV patients (recurrent and naïve CNV groups), the aqueous humor levels of IL-6 and IL-8 significantly correlated with the size of CNV (rho=0.692, p=0.001 and rho=0.745, p<0.001, respectively).

Based on their study findings, the investigators determined that levels of VEGF measured in the aqueous humor were significantly related to the disease activity of CNV in AMD. Moreover, IL-2, IL-6, IL-8 and tumor necrosis factor-alpha may be related to the activity of CNV.

Source: Roh MI, Kim HS, Song JH, et al. Concentration of cytokines in the aqueous humor of patients with naive, recurrent and regressed CNV associated with AMD after bevacizumab treatment. Retina 2009;Mar 2 [Epub ahead of print].