Biologics License Application Submitted to FDA for VEGF TRAP-EYE for Treatment of Wet AMD In a recent news release, Regeneron Pharmaceuticals, Inc. announced that it submitted a Biologics License Application (BLA) to the U.S. FDA for VEGF Trap-Eye for the treatment of the neovascular form of age-related macular degeneration (AMD). pSivida Shares 36-Month Results of Completed Phase 3 FAME Study of Iluvien pSivida Corp. recently announced month 36, top-line readout results for the FAME Study, prepared by its licensee, Alimera Sciences, Inc. And More...

Treatment of ROP with IVB

A prospective, controlled, randomized, stratified, multicenter trial was conducted to assess intravitreal bevacizumab (IVB) monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity (ROP).

Infants were randomly assigned to receive IVB (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally, and the primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks' postmenstrual age.

A total of 150 infants (300 eyes) were enrolled; 143 infants survived to 54 weeks' postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. It was noted that ROP recurred in 4 infants in the bevacizumab group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], p=0.002). A significant treatment effect was found for zone I ROP (p=0.003) but not for zone II disease (p=0.27).

IVB monotherapy, as compared with conventional laser therapy, in infants with stage 3+ ROP showed a significant benefit for zone I but not zone II disease. Futhermore, development of peripheral retinal vessels continued after treatment with IVB, but conventional laser therapy led to permanent destruction of the peripheral retina. This trial was too small to assess safety.

Source: Mintz-Hittner HA, Kennedy KA, Chuang AZ; for the BEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med 2011;364(7):603–615.

Bevacizumab and ROP: Editorial

This editorial discusses the use of bevacizumab in the treatment of retinopathy of prematurity (ROP), with particular focus on the study above by Mintz-Hittner and colleagues, which compares intravitreal bevacizumab (IVB) to conventional laser therapy. It points out that in comparing IVB to an effective, established treatment, there are three concerns: efficacy, safety and practicality and that with regard to the Mintz-Hittner, et al. study, as compared with conventional laser therapy in treating patients with zone I ROP, IVB represents a true breakthrough in disease management.

The editorial also notes that the safety of therapy for ROP involves not only the eye, but also potentially profound systemic issues. Bearing in mind the pharmacokinetics of bevacizumab, the extensive experience with adults taking this drug and the study by Mintz-Hittner and colleagues, it seems reasonable to assume that IVB is safe; however, continued vigilance will be important as use of the drug continues. With respect to ocular health with the use of IVB, the editorial mentions that timing of the injection is critical, as injection too early in the disease process may interfere with necessary retinal vascularization and injection too late may accelerate the cicatricial phase of ROP and lead to early retinal detachment.

In light of previous work and its confirmation in a robust clinical trial, the use of IVB as monotherapy is superior to laser therapy in treating zone I ROP and is possibly superior in treating posterior zone II disease, the editorial concludes. The author goes on to speculate that IVB therapy will prove to be at least equal to laser therapy in clinical effectiveness for most forms of ROP and that, as our experience with the drug grows, its indications and relative contraindications will be refined. In the meantime, IVB should become the treatment of choice for zone I ROP.

Source: Reynolds JD. Bevacizumab for retinopathy of prematurity. N Engl J Med 2011;364(7):677–678.

Effects and Complications Associated with Bevacizumab for ROP Treatment

Researchers in Taiwan investigated the effects and complications of the anti-vascular endothelial growth factor (VEGF) agent bevacizumab in the treatment of retinopathy of prematurity (ROP) in Taiwanese patients.

A total of 27 (18 male and 9 female) patients (49 eyes) from 4 medical centers across Taiwan participated in this multicenter, retrospective case series study. The study included patients receiving intravitreal injections of bevacizumab (IVB) (0.625 mg) for the treatment of ROP between 2007 and 2009 at 4 major medical centers in Taiwan. The study researchers analyzed the effects and complications associated with this treatment and followed patients for at least 6 months after bevacizumab injection. Regression of ROP and the complications associated with the injection of bevacizumab served as the main outcome measures.

According to the researchers, mean gestational age and birth weight were 26.0 ± 2.4 weeks and 971.6 ± 589.6 g, respectively. They noted that there were 41 eyes (23 patients) with stage 3 ROP, 6 eyes (3 patients) with stage 4A ROP and 2 eyes (1 patient) with stage 5 ROP. All of the eyes received only a single injection of IVE and the mean injection time was 36.8 ± 2.6 weeks postmenstrual age for eyes with stage 3 ROP. The researchers reported that a total of 37 of 41 eyes (90%) with stage 3 ROP regressed after bevacizumab injection only and that 4 eyes (10%) required additional laser treatment to regress the ROP. Of 6 eyes (3 patients) with stage 4A ROP, the researchers observed that 2 eyes (1 patient; 33%) regressed after bevacizumab injection and that 4 eyes (67%) regressed after bevacizumab injection and subsequent vitrectomy. The 2 eyes with stage 5 ROP exhibitied decreased vascular tortuosity after bevacizumab injection, but the retina failed to reattach after vitrectomy surgeries. Major complications included vitreous or pre-retinal hemorrhage in 4 eyes (8%) and transient vascular sheathing in 2 eyes (4%).

Source: Wu WC, Yeh PT, Chen SN, et al. Effects and complications of bevacizumab use in patients with retinopathy of prematurity: a multicenter study in Taiwan. Ophthalmol 2011;118(1):176–183.

Intravitreal Techniques of U.S. Retinal Specialists

Scientists used a questionnaire survey to describe the intravitreal injection technique practice patterns of retinal specialists in the United States from April 8, 2010 to April 21, 2010. They contacted all members of the American Academy of Ophthalmology who self-categorized as “Retinal/Vitreous Surgery” by e-mail to complete an anonymous, 20-question, Internet-based survey and found that retinal specialists in the United States participate in a range of techniques for the care before, during and after intravitreal injections.

A total of 765 retinal specialists (44%) responded to the survey. Most respondents wear gloves (58%) and use an eyelid speculum (92%) when performing an intravitreal injection; more than 99% use povidone-iodine preinjection. According to the study scientists, the majority measure the injection site from the limbus (56%) and inject straight into the vitreous cavity (96%); most do not displace the conjunctiva (83%). They found that 72% routinely assess postinjection optic nerve perfusion, primarily by gross visual acuity measurement (32%). While nearly one-third of participants use prophylactic topical antibiotics preinjection, more than two-thirds use topical antibiotics postinjection. Furthermore, 46% perform bilateral simultaneous intravitreal injections. The majority of respondents use a 30-gauge needle for the injection of ranibizumab (78%) and bevacizumab (60%). However, respondents use both a 27- and 30-gauge needle for the injection of triamcinolone acetonide.

The researchers determined that bevacizumab injection seems effective and well tolerated in some cases of ROP, especially in stage 3 ROP. Ocular complications could result from the injection of bevacizumab in pediatric eyes.

Source: Green-Simms AE, Ekdawi NS, Bakri SJ. Survey of intravitreal injection techniques among retinal specialists in the United States. Am J Ophthalmol 2011;151(2):329–332.

Differential Effect of AMD-Associated Genetic Variants on Risk of CNV and GA

The following genetic association multi-center study aimed at determining whether genetic variants that have been associated with age-related macular degeneration (AMD) have a differential effect on the risk of choroidal neovascularization (CNV) and geographic atrophy (GA).

A total of 749 participants with GA and 3,209 participants with CNV were derived from four AMD studies with similar procedures from Tufts Medical Center, the Age-Related Eye Disease Study, University of Utah and Hospital Intercommunal de Creteil. It was reported that AMD grade was assigned based on fundus photography and examination using the clinical age-related maculopathy staging system. All samples were genotyped for single nucleotide polymorphisms (SNPs) previously associated with AMD and allele frequencies were compared between participants with CNV and GA using PLINK within each cohort and Mantel-Haenszel meta-analysis was performed to combine odds ratio (OR). Differences in allele frequencies between participants with GA and CNV served as the main outcome measures.

It was observed that the frequency of the T allele of ARMS2/HTRA1 rs10490924 was significantly higher in participants with CNV than in those with GA (OR, 1.37; 95% confidence interval, 1.21–1.54; p value = 4.2 x 10[–7]). This result remained statistically significant when excluding individuals who had GA in 1 eye and CNV in the contralateral eye (p=2.2 x 10[–4]). None of the other SNPs showed a significant differential effect for CNV vs geographic atrophy, including CFH, C2/CFB, C3, CFI, LIPC and TIMP3.

In conclusion, genetic variation at the ARMS2/HTRA1 locus confers a differential risk for CNV vs GA in a well-powered sample.

Source: Sobrin L, Reynolds R, Fagerness J, et al. ARMS2/HTRA1 locus can confer differential susceptibility to the advanced subtypes of age-related macular degeneration. Am J Opthalmol 2011s;151(2):345–352.

IS-OS Junctional Layer Integrity and Related Retinal Sensitivity in AMD

Scientists sought to investigate a relationship between the inner segment-outer segment (IS-OS) junctional layer integrity and the overlying retinal sensitivity assessed by Spectral OCT/SLO (spectral-domain optical coherence tomography, SD-OCT) and microperimetry testing in patients with dry and wet forms of age-related macular degeneration (AMD).

They performed SD-OCT examination and microperimetry in 55 eyes of 43 consecutive patients with AMD and registered microperimetry maps onto 3-D retinal tomography maps, then performed point-to-point analysis of correlation between microperimetric retinal sensitivities and corresponding status of the underlying IS-OS junctional layer. The scientists also performed an analysis of correlation between the best-corrected visual acuity and the integrity of IS-OS layer in the center of the fovea.

They found that retinal sensitivity was inversely and strongly correlated with the integrity of IS-OS layer in both dry and wet forms of AMD (correlation coefficient [r] = –0.75 [95% confidence interval, 0.49–0.88], p<0.001, and –0.79 [95% confidence interval, 0.61–0.89], p<0.001, respectively). The correlation between the best-corrected visual acuity and the integrity of IS-OS layer in the center of fovea was less significant (r= –0.58 [95% confidence interval, 0.19–0.79], p=0.02, for dry AMD, and r= –0.6 [95% confidence interval, 0.32–0.78], p=0.015, for wet AMD).

Retinal sensitivity consistently correlated with the status of underlying IS-OS junctional layer in both dry and wet forms of AMD, the scientists found. They also concluded that loss of IS-OS layer is significantly associated with poor retinal sensitivity, assessed by microperimetry and that, compared with visual acuity, functional testing with microperimetry appears to more consistently correlate with changes in the outer retina, such as IS-OS junctional integrity, especially in patients with wet AMD.

Source: Landa G, Su E, Garcia PM, et al. Inner segment-outer segment junctional layer integrity and corresponding retinal sensitivity in dry and wet forms of age-related macular degeneration. Retina 2011;31(2):364–370.

Impact of Verteporfin PDT for Polypoidal Choroidal Vasculopathy on Subfoveal Retinal and Choroidal Thickness

Investigators in a Japanese retrospective, comparative series evaluated the morphologic retinal and choroidal changes after verteporfin photodynamic therapy (PDT) with and without ranibizumab for polypoidal choroidal vasculopathy using spectral-domain optical coherence tomography (SD-OCT).

They used the enhanced depth imaging optical coherence tomography (OCT) technique to measure the subfoveal retinal and choroidal thicknesses before and after treatment. They examined 27 eyes with polypoidal choroidal vasculopathy retrospectively and treated 16 eyes with PDT monotherapy (PDT group); 11 eyes were treated with PDT after intravitreal ranibizumab injection (ranibizumab plus PDT group).

The investigators noted that the polypoidal lesions regressed in all cases at 3 months and that the mean retinal thickness, including the retinal detachment, increased from 401 ± 157 µm before treatment to 506 ± 182 µm 2 days after PDT (p<.001) and decreased to 365 ± 116 µm by 1 week after treatment (p=.03) and 265 ± 127 µm by 6 months after treatment (p<.001). They also observed that the mean choroidal thickness increased from 269 ± 107 µm before treatment to 336 ± 96 µm 2 days after PDT treatment (p<.001 compared with baseline) and decreased to 262 ± 96 µm by 1 week after treatment (p=.24) and 229 ± 104 µm by 6 months (p<.001). Although the choroidal thickness showed a similar trend with both therapies, the retinal thickness in the ranibizumab plus PDT group remained thinner than that in the PDT group until 6 months after treatment.

The study investigators found that PDT was associated with decreased retinal and choroidal thicknesses and that combination therapy reduced the transient exudation after PDT in some cases, and monthly intravitreal ranibizumab injections maintained retinal thinning and seemed to improved vision better than PDT monotherarpy.

Source: Maruko I, Iida T, Sugano Y, et al. Subfoveal retinal and choroidal thickness after verteporfin photodynamic therapy for polypoidal choroidal vasculopathy. Am J Ophthalmol 2011;Feb 4 [Epub ahead of print].

Microperimetric Changes Following PDT for CSC

Researchers in Turkey conducted the following interventional case series to evaluate the effect of half-dose verteporfin photodynamic therapy (PDT) on macular function in cases of central serous chorioretinopathy (CSC).

They included a total of 24 eyes from 24 cases of CSC in the study and in each eye, at baseline and 1, 3 and 6 months after half-dose PDT, assessed logMAR best-corrected visual acuity (BCVA); central 10-degree, 20-degree and paracentral 10-degree to 20-degree retinal sensitivity; and also mean retinal sensitivity results for each case over the area that was treated with half-dose PDT (PDT spot area) by MP-1 microperimetry and optical coherence tomography (OCT) foveal morphologic changes. The MP-1 microperimetry sensitivity map was overlaid onto an indocyanine green angiography image recorded on a Heidelberg scanning laser ophthalmoscope using dedicated MP-1 software to evaluate the PDT laser spot area.

The study researchers noted that after treatment, BCVA and central 10-degree, 20-degree, paracentral 10-degree to 20-degree and PDT laser spot area retinal sensitivity were improved significantly. In OCT in 20 of 24 eyes (83%), they reported that subretinal fluid (SRF) was resolved 1 month after half-dose PDT and at 3 and 6 months after treatment, SRF was resolved at all eyes. None of the patients in this study developed any systemic or ocular adverse events associated with verteporfin treatment.

Half-dose verteporfin PDT induced a significant increase in central 10-degree, 20-degree, paracentral 10-degree to 20-degree and also PDT laser spot area retinal sensitivity over 6 months in cases of CSC, the researchers found.

Source: Senturk F, Karacorlu M, Ozdemir H, et al. Microperimetric changes after photodynamic therapy for central serous chorioretinopathy. Am J Opthalmol 2011;151(2):303–309.

Comparison of Intravitreal Triamcinolone Acetonide and Bevacizumab for Macular Edema Secondary to CRVO

Researchers compared the efficacy and safety of intravitreal triamcinolone acetonide (IVT) versus intravitreal bevacizumab (IVB) for the treatment of macular edema (ME) secondary to central retinal vein occlusion (CRVO) in the following prospective, consecutive, clinical interventional study.

They randomized a total of 31 consecutive patients (32 eyes) with ME associated with CRVO to 2 groups and treated 16 eyes with intravitreal injection of 4 mg/0.1 mL preservative-free triamcinolone acetonide; 16 eyes received IVB 1.25 mg/0.05 mL. They gave patient additional injections if they had ME as determined by optical coherence tomography (OCT) 3 months after the first treatment or visual acuity loss of at least 2 lines in Snellen chart and during the 9-month follow-up period, recorded best-corrected visual acuity (BCVA), slit lamp biomicroscopy, intraocular pressure (IOP), fundus fluorescein angiography, optical coherence tomography, the number of required injections and adverse events.

BCVA was significantly improved at 2 weeks and 1, 3, 6 and 9 months after injection in both the IVT and IVB groups, the researchers noted, but they found no statistical difference between the 2 treatment groups during the 9-month follow-up period. They also reported that the mean central macular thickness decreased at 1, 3, 6 and 9 months after injection within each treatment group, and no statistical difference was found between the 2 treatment groups at any time during the follow-up period (p>0.05). According to the researchers, patients who received IVT treatment appeared to have quicker visual recovery and improved central macular thickness at Week 2 compared with those who received IVB treatment. Five of 16 eyes in the IVT group and 12 of 16 eyes in the IVB group required a repeated injection because of recurrent ME or unresolved intraretinal or subretinal fluid. The mean number of treatment was 1.31 ± 0.48 in the IVT group, as compared with 2.38 ± 1.04 in the IVB group. The researchers found significant IOP increase only in the IVT group, six patients received topical IOP-lowering medication, one patient required trabeculectomy and premacular membranes were developed in 2 patients in the IVT group.

They determined that both IVT and IVB treatments can effectively improve BCVA and reduce central macular thickness in patients with ME secondary to CRVO without systemic side effects; they found no statistical differences in either BCVA or mean central macular thickness measurement between the two treatment groups. Both the effect of triamcinolone acetonide and that of bevacizumab were not permanent, and less injections were performed in the IVT group; however, triamcinolone acetonide causes more adverse events than bevacizumab.

Source: Ding X, Li J, Hu X, et al. Prospective study of intravitreal triamcinolone acetonide versus bevaciumab for macular edema secondary to central retinal vein occlusion. Retina 2011;Feb 2 [Epub ahead of print]. DOI: 10.1097/IAE.0b013e3181f4420d.

Changes in Central Macular Thickness Following Intravitreous Triamcinolone or Bevacizumab in DME or RVO

In the following nonrandomized, interventional study, investigators evaluated the immediate changes after intravitreous triamcinolone acetonide or intravitreous bevacizumab (IVB) in diabetic macular edema (DME). They determined that factors responsive to triamcinolone acetonide, other than vascular endothelial growth factor, might play an important role in pathogenesis of DME compared with retinal vein occlusion (RVO).

The investigators included type 2 diabetic patients in the study. They injected intravitreous triamcinolone acetonide (4 mg) for 22 eyes with DME and IVB (1.25 mg) for 18 eyes with DME and evaluated the early time-dependent changes of central macular thickness by optical coherence tomography before and from 1 hour to 1 month after intervention. The investigators also tested IVB in patients with RVO as a control of non-DME. They also examined visual acuity.

Compared with the baseline, the study investigators found that central macular thickness of eyes with DME decreased significantly 1 hour after intravitreous triamcinolone acetonide (p<0.05, Wilcoxon signed rank test), while it did not significantly until 24 hours after IVB. They observed the decrease in central macular thickness significantly from 3 hours after IVB in RVO (p<0.05, Wilcoxon signed rank test), and it was more evident in RVO than DME following IVB. Furthermore, visual acuity improved significantly in DME with intravitreous triamcinolone acetonide or IVB at 1 month (p<0.01 and p<0.05, respectively, Wilcoxon signed rank test).

Although no conclusion can be drawn, immediate decrease in central macular thickness after intravitreous triamcinolone acetonide might indicate the possible involvement of a nongenomic pathway of triamcinolone acetonide action.

Source: Sonoda Y, Arimura N, Shimura M, Sakamoto T. Early change of central macular thickness after intravitreous triamcinolone or bevacizumab in diabetic macular edema or retinal vein occlusion. Retina 2011;31(2):290–297.

Role of Intravitreal TNF Inhibitors in the Treatment of Refractory DME

To report the short-term visual and anatomical outcomes after intravitreal injections of two different tumor necrosis factor α inhibitors in eyes with refractory diabetic macular edema (DME), investigators conducted an interventional, retrospective, multicenter study of 39 eyes with refractory DME that were injected with adalimumab (n=5 for 2 mg) or infliximab (n=15 for 1 mg; n=19 for 2 mg). Best-corrected visual acuity and the central macular thickness at 3 months of follow up were the main outcome measures.

The investigators reported that in the 1-mg infliximab group, the logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) improved from 1.49 ± 058 at baseline to 1.38 ± 0.56 at 3 months (p=0.6991). They found that in the 2-mg infliximab group, the logMAR BCVA worsened from 0.76 ± 0.54 to 1.03 ± 0.69 at 3 months (p=0.5995). In the adalimumab group, the logMAR BCVA improved from 1.44 0.77 to 1.08 ± 0.85 at 3 months (p=0.2500). According to the study investigators, the central macular thickness in the 1-mg infliximab group decreased from 459 ± 125 µm at baseline to 388 ± 131 µm at 3 months (p=0.1178). They also observed that in the 2-mg infliximab group, the central macular thickness remained unchanged from 378 ± 97 µm at baseline to 349 ± 118 µm at 3 months (p=0.2162). In the adalimumab group, the central macular thickness remained unchanged from 521 ± 163 µm at baseline to 526 ± 390 µm at 3 months (p=0.1250). No systemic side effects were reported in any of the patients; however, laboratory markers for autoimmunity were not done. None of the eyes injected with either adalimumab or 1 mg of infliximab had adverse ocular events and in the 2-mg infliximab group, 42% (8 of 19) of eyes developed severe uveitis. Three of these eyes (37.5%) required pars plana vitrectomy and the uveitis in the remaining five eyes resolved with topical steroid therapy.

Both intravitreal adalimumab and infliximab do not appear to benefit eyes with refractory diabetic macular edema, the investigators concluded. Intravitreal injections of infliximab may elicit a severe intraocular inflammatory reaction.

Source: Wu L, Hernandez-Bogantes E, Roca JA, et al. Intravitreal tumor necrosis factor inhibitors in the treatment of refractory diabetic macular edema: a pilot study from the Pan-American Collaborative Retina Study Group. Retina 2011;31(2):298–303.

Ocular Side Effects of Peribulbar Injections of Triamcinolone Acetonide for DME

Researchers reported on intraocular pressure (IOP) and cataract progression through 2 years in 96 eyes with diabetic macular edema (DME) randomized to focal/grid photocoagulation, 20 mg triamcinolone acetonide anterior injection, anterior injection followed by laser, 40 mg triamcinolone acetonide posterior injection or posterior injection followed by laser to evaluate long-term effects of anterior and posterior pierbulbar injections of triamcinolone acetonide on IOP elevation and cataract development.

The study researchers recorded that IOP increased from baseline by ≥10 mmHg at ≥1 visit through 2 years in 2 eyes (8%) in the laser group, 11 eyes (31%) in the anterior groups and 6 eyes (17%) in the posterior groups and that, among phakic eyes at baseline, 0; 5 (17%); and 1 (3%) in the 3 groups, respectively, underwent cataract surgery before the 2-year visit.

Based on this small, randomized trial, it appeared to the researchers that over 2 years, anterior peribulbar triamcinolone acetonide injections are associated with an increased incidence of IOP elevation and an increased risk of cataract development compared with laser or posterior peribulbar injections. The association of posterior injections with IOP elevation is less certain. Although the study involved eyes with DME, the results should be relevant to other conditions treated with peribulbar corticosteroids.

Source: Chew EY, Glassman AR, Beck RW, et al; for the Diabetic Retinopathy Clinical Research Network. Ocular side effects associated with peribulbar injections of triamcinolone acetonide for diabetic macular edema. Retina 2011;31(2):284–289.

Link Between VA in Diabetic Retinopathy and Pathomorphology, Photoreceptor Status and Retinal Thickness

The authors of this retrospective, observational Japanese case series sought to evaluate whether visual acuity (VA) is associated with pathologic changes in morphology (pathomorphology), macular thickness and the status of external limiting membrane (ELM) in diabetic retinopathy (DR).

They retrospectively analyzed 125 consecutive eyes of 73 patients with DR. No patients had been treated for diabetic macular edema, and all had Spectralis optical coherence tomography (OCT) images. The authors evaluated the pathomorphology, qualitatively evaluated the status of ELM and cystic changes and measured the retinal thickness. Additionally, they investigated the correlation with logarithm of the minimal angle of resolution (logMAR).

They classified 3 types of pathomorphology at the presumed fovea: cystoid macular edema (CME type, n=20), serous retinal detachment (SRD type, n=21) and the absence of either CME or SRD (diffuse type, n=84). They reported that the mean logMAR VA with the CME type (0.460 ± 0.301) was significantly worse than with the SRD type (0.222 ± 0.178; p.=.004) or diffuse type (0.149 ± 0.260; p<.001). With CME type and diffuse type, a disrupted ELM or parafoveal thickening was significantly correlated with poor VA; these correlations were not found with the SRD type. The study authors noted that 79 of 104 eyes with CME type or diffuse type presented intact ELM and showed the significant correlation between logMAR and the parafoveal thickness or cystic changes, although these parameters were not associated with logMAR VA in 25 eyes with disrupted ELM.

In conclusion, the pathomorphology and photoreceptor status at the fovea and retinal edema in the parafovea are correlated with the VA in DR.

Source: Murakami T, Nishijima K, Sakamoto A, et al. Association of pathomorphology, photoreceptor status, and retinal thickness with visual acuity in diabetic retinopathy. Am J Ophthalmol 2011;151(2):310–317.

Relationship Between Cilioretinal Arteries in Diabetic Eyes and Retinal Blood Flow Velocity and Occurrence of DME

The main purpose of this study was to investigate the relationship between occurrence of cilioretinal arteries and macular edema in diabetic eyes in terms of retinal blood flow characteristics revealed by the Retinal Function Imager (RFI). Other standard imaging techniques, such as fundus photography, fluorescein angiography and spectral-domain optical coherence tomography (SD-OCT)/scanning laser ophthalmoscopy (SLO) were also used along with the RFI. The additional purpose of this study was to look for the evidence of cilioretinal-retinal collaterals using the RFI.

According to the authors of this study, patients with a diagnosis of diabetic retinopathy were included and all patients underwent fundus photography, fluorescein angiography, spectral-domain optical coherence tomography and imaging using RFI. They recognized the presence of cilioretinal artery (CilRA) using color/red-free fundus photographs, fluorescein angiography and RFI. They formed two groups in this study according to the presence (CilRA group) or absence (NoCilRA group) of cilioretinal artery or arteries in the study study eye.

A total of 39 eyes with diabetic retinopathy (DR) were included. The authors identified cililoretinal artery in 15 eyes (38%). In the CilRA group, they observed SD-OCT evidence of macular edema in 13 of 15 eyes (87%), whereas in the NoCilRA group, they observed macular edema on SD-OCT in 7 of 24 eyes (29%). Mean blood flow velocities in retinal arteries and veins were significantly higher in diabetic eyes with cilioretinal artery (p=0.04 and p=0.005, respectively) and mean blood velocity in cilioretinal arteries was significantly higher in comparison with the mean arterial blood velocity (p=0.03). In the CilRA group, the authors of the study detected cilioretinal-retinal collaterals, assessed by RFI, in 4 of 15 eyes (27%) with cilioretinal arteries. In the NoCilRA group, they found that mean blood velocity in retinal veins was significantly higher in eyes with macular edema in comparison with those without macular edema (p=0.03).

In conclusion, using the RFI in conjunction with standard fundus imaging techniques, the presence of cilioretinal artery in diabetic eyes was found to be associated with increased retinal blood flow velocity and increased occurrence of diabetic macular edema. The authors also noted the occurrence of cilioretinal-retinal collaterals; however, the pathophysiologic significance of this finding requires further investigation.

Source: Landa G, Amde W, Haileselassie Y, Rosen R. Cilioretinal arteries in diabetic eyes are associated with increased retinal blood flow velocity and occurrence of diabetic macular edema. Retina 2011;31(2):304–311.

Effect of Refractive Error and Axial Length on Retinal Vessel Geometric Characteristics

To evaluate the influence of refractive error and axial length (AL) on retinal vascular network geometry measurements in an adult Asian population, the following population-based, cross-sectional study on 2,882 persons with diabetes in the Singapore Malay Eye Study was conducted.

Spherical equivalent refraction was assessed using an autokeratorefractometer and subjective refraction and AL retinal vascular caliber, tortuosity and branching characteristics were quantified from retinal fundus photographs using a semi-automated, computer-assisted program according to a standardized protocol.

It was noted that in multivariate analyses adjusting for age, sex, education, smoking, blood pressure, diabetes status and antihypertensive medication use, longer AL and more myopic refraction were associated with narrower retinal arterioles and venules (p≤0.001 for all) and less tortuous (straighter) arterioles (p<0.001 for both). Longer AL and more myopic refraction were also associated with increased branching coefficients in both arterioles (p<0.001 for both) and venules (p=0.02 and p<0.001, respectively). Moreover, longer AL and more myopic refraction were associated with more acute branching angles in arterioles (p<0.001 for both) but not venules.

To conclude, myopic refractive errors and longer AL are associated with narrower retinal arterioles and venules, less tortuous arterioles and increased branching coefficients in both arterioles and venules. These findings provide insights into ocular blood flow in myopia and also suggest that future studies evaluating these retinal parameters should account for the influence of AL and refractive error.

Source: Lim LS, Cheung CY, Lin X, et al. Influence of refractive error and axial length on retinal vessel geometric characteristics. Invest Ophthalmol Vis Sci 2011;52(2):669–678.

Treatment of Hereditary Retinal Dystrophy with Intravitreal Injection of Autologous Bone Marrow-Derived Mononuclear Cells

A prospective, Phase 1, nonrandomized, open-label study including 3 patients with retinitis pigmentosa (RP) and 2 patients with cone-rod dystrophy and an Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA) of 20/200 or worse sought to evaluate the short-term (10 months) safety of a single intravitreal injection of autologous bone marrow-derived mononuclear cells in patients with RP or cone-rod dystrophy.

Evaluations including BCVA, full-field electroretinography, kinetic visual field (Goldman), fluorescein and indocyanine green angiography and optical coherence tomography (OCT) were performed at baseline and 1, 7, 13, 18, 22 and 40 weeks after intravitreal injection of 10 x 106 autologous bone marrow-derived mononuclear cells (0.1 mL) into 1 study eye of each patient.

No adverse event associated with the injection was observed and a 1-line improvement in BCVA was measured in 4 patients 1 week after injection and was maintained throughout follow up. It was also reported that three patients showed undetectable electroretinography responses at all study visits, while 1 patient demonstrated residual responses for dark-adapted standard flash stimulus (a wave-amplitude approximately 35 µV), which remained recordable throughout follow up, and 1 patient showed a small response (a wave amplitude approximately 20 µV) recordable only at Weeks 7, 13, 22 and 40. Visual fields showed no reduction (with a Goldman Standard V5e stimulus) for any patient at any visit. No other changes were observed on OCT or fluorescein and indocyanine green angiograms.

In conclusion, intravitreal injection of autologous bone marrow-derived mononuclear cells in eyes with advanced RP or cone-rod dystrophy was associated with no detectable structural or functional toxicity over a period of 10 months. It was noted that further studies are required to investigate the role, if any, of autologous bone marrow-derived mononuclear cell therapy in the management of retinal dystrophies.

Source: Siqueira RC, Messias A, Voltarelli JC, et al. Intravitreal injection of autologous bone marrow-derived mononuclear cells for hereditary retinal dystrophy: a phase I trial. Retina 2011;Feb 2 [Epub ahead of print]. DOI: 10.1097/IAE.0b013e3181f9c242.