Second Human Subject Study Using Integrin Peptide Therapy to Treat Neovascular Eye Disease Initiated According to a press release from Allegro Ophthalmics, LLC, the company has commenced its second human subject study using Integrin Peptide Therapy... Favorable Interim Results Reported from Quark's Phase I Clinical Study of QPI-1007 for Ocular Neuroprotection Quark Pharmaceuticals, Inc. has reported interim results from the first two cohorts of its Open Label, first-in-human Phase I clinical study of QPI-1007... And More...

Aqueous Humor Levels of VEGF Before and After Intravitreal Bevacizumab in Type 3 Versus Type 1 and 2 Neovascularization

To determine the aqueous levels of vascular endothelial growth factor (VEGF) in patients with type 3 neovascularization (NV) secondary to age-related macular degeneration (AMD) and to compare the levels of those with type 1 and 2 NV secondary to AMD before and after administration of intravitreal bevacizumab (IVB), the following prospective, case-control study was performed.

Aqueous samples were collected from 29 eyes of 29 patients with untreated wet AMD at baseline (day of the first IVB), month 1 (day of the second IVB) and month 2 (day of the third IVB). Among them, 10 eyes presented with type 1, 9 with type 2 and 10 with type 3 NV. A group of 14 aqueous samples from 14 patients who underwent cataract surgery without other ocular or systemic disease comprised the controls. Main outcome measures included best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes after IVB. Additionally, levels of VEGF were determined by commercially available enzyme-linked immunosorbent assay kits.

It was observed that VEGF concentrations in aqueous humor at baseline were higher in patients with type 3 NV when compared to controls (p=.0001) and type 1 and 2 NV patients (p=.002 and p=.0001, respectively). At month 1, levels of VEGF were significantly reduced compared to baseline (p<.05) and significantly lower compared to the controls (p<005) in each NV group. These low levels were maintained at the 2-month interval. BCVA significantly improved in type 1 and 2 NV groups (p<.05). CMT significantly reduced in each NV group compared to baseline (p<.05).

To conclude, in eyes with untreated wet AMD, aqueous levels of VEGF are significantly higher in type 3 NV than in type 1 or 2 NV. Regardless of the type of NV, aqueous VEGF levels significantly reduce 1 month after IVB as compared to both the baseline measurements and the values recorded in age-matched controls. These decreases are maintained at 2 months after administering a second IVB 30 days after the initial injection.

Source: Dell'Omo R, Cassetta M, Dell'Omo E, et al. Aqueous humor levels of vascular endothelial growth factor before and after intravitreal bevacizumab in type 3 versus type 1 and 2 neovascularization. A prospective, case-control study. Am J Ophthalmol. 2012;153(1):155–161.

Incidence of Tachyphylaxis During Treatment of Exudative AMD with Ranibizumab

Scientists in Denmark conducted a retrospective review of cases to determine whether tachyphylaxis occurs during treatment with ranibizumab (Lucentis, Genentech, Inc.) for exudative age-related macular degeneration (AMD).

They evaluated the treatment results of 1,076 eyes (976 patients) treated with ranibizumab for exudative AMD to identify patients with a potential tachyphylactic response. The participants had to have a minimum of 12 months follow up. The scientists defined tachyphylaxis as a lack of response to the drug at the time of reactivation of choroidal neovascularization (CNV) in patients who had responded to the initial treatment. They considered it a lack of response to ranibizumab if they observed a decrease in vision and an increase in central retinal thickness (CRT) despite repeated injections. Hence, they did not consider a stabilization in vision and/or stabilization in CRT during treatment tachyphylaxis, and other unfavorable responses such as a tear in the retinal pigment epithelium and therefore, they also did not consider a decrease in vision during treatment as tachyphylaxis. Additionally, they identified every patient in this cohort who has had an injection-free interval after primary inactivation of CNV and who has received retreatment at a later stage. In this population, the scientists identified and characterized those cases that did not respond to retreatment. They noted that main outcome measures were number of patients who developed tachyphylaxis after treatment with ranibizumab.

They discovered that 20 patients (2%) developed tachyphylaxis during their treatment.

Tachyphylaxis can occur during the treatment of exudative AMD with ranibizumab. The precise mechanism for the development of tachyphylaxis is unclear. Both local and systemic factors might be involved.

Source: Eghøj MS, Sørensen TL. Tachyphylaxis during treatment of exudative age-related macular degeneration with ranibizumab. Br J Ophthalmol. 2012;96(1):21–23.

Role of Bevacizumab and Ranibizumab Tachyphlyaxis in the Treatment of Choroidal Neovascularization

To evaluate the effect of switching to bevacizumab or ranibizumab after developing tachyphylaxis during anti-vascular endothelial growth factor (VEGF) therapy for choroidal neovascularization (CNV) the authors of this study reviewed the records of all patients who received both drugs for treatment of CNV to identify those who developed tachyphylaxis, defined as optical coherence tomography (OCT) evidence of initial decreased exudation followed by lack of further reduction or an increase in exudation. Signs of exudation included subretinal fluid (SRF), pigment epithelial detachment (PED) and/or cystoid macular edema (CME).

The authors included 26 eyes. A total of 10 were initially treated with bevacizumab and then changed to ranibizumab for persistent SRF, PED and/or CME. Of these, seven had occult CNV and three had predominantly classic CNV. One eye in the occult CNV group did not respond after being switched to ranibizumab, the authors noted. They also found that six eyes had a positive therapeutic response, after one injection in four eyes, and after two or three injections in one eye each. They reported that in the classic group, two responded to ranibizumab and one did not. Sixteen eyes were initially treated with ranibizumab before changing to bevacizumab. Of these, 15 had occult CNV and 1 was predominantly classic. Furthermore, three of the 16 eyes failed to respond to bevacizumab; 6 improved after one injection and 5 improved after two injections.

The authors concluded that patients with CNV who develop tachyphylaxis to ranibizumab or bevacizumab may respond to another anti-VEG drug. The majority of cases (81%) in this series demonstrated at least some response after switching therapies.

Source: Gasperini JL, Fawzi AA, Khondkaryan A, et al. Bevacizumab and ranibizumab tachyphylaxis in the treatment of choroidal neovascularization. Br J Ophthalmol. 2012;96(1):14–20.

Pharmacokinetic Rationale for 2-Week Dosing of Intravitreal Ranibizumab, Bevacizumab and Aflibercept (VEGF Trap-Eye)

While monthly dosing with inhibitors of vascular endothelial growth factor (VEGF) results in stable or improved visual acuity in most patients with neovascular age-related macular degeneration (AMD), a minority of patients show little if any response to therapy with persistent or worsening macular fluid. In this study, pharmacokinetic modeling was performed to determine whether more frequent dosing with anti-VEGF drugs could be theoretically beneficial.

A mathematical model comparing the time-dependent relative binding activities of ranibizumab, bevacizumab and aflibercept (VEGF Trap-Eye) was used to determine the theoretical peak and trough binding activities when the drugs were injected every 14 days and every 28 days. The intravitreal half-lives of ranibizumab, bevacizumab and the VEGF Trap-Eye were estimated to be 3.2, 5.6 and 4.8 days, respectively. It was also noted that the relative molar binding activities of ranibizumab, bevacizumab and the VEGF Trap-Eye used in the analyses were 1, 0.05 to 0.2 and 140, respectively. Additionally, the expected peak and trough binding activities for ranibizumab, bevacizumab and VEGF Trap-Eye were calculated and dosing every 2 weeks was performed on selected patients who had a poor response to monthly therapy.

It was reported that dosing of a drug every 2 weeks resulted in markedly improved trough binding activity, but had little impact on the peak binding activity when calculated through Day 28. Also, that the dosing of bevacizumab every 2 weeks resulted in trough binding levels that were superior to monthly dosing with ranibizumab at a dose of 0.5 mg and potentially superior to the levels achieved when ranibizumab was dosed monthly at a dose of 2.0 mg. It was also noted that the VEGF Trap-Eye displayed superior binding levels for both peak and trough levels even when compared with ranibizumab doses given every 2 weeks. Two case reports demonstrate the clinical usefulness of dosing with anti-VEGF therapy every 2 weeks in eyes with VEGF-dependent macular fluid appearing to be refractory to monthly dosing.

To conclude, the theoretical increase in trough binding levels when anti-VEGF drugs are dosed every 2 weeks most likely explains the clinical benefit observed in patients who received bi-weekly injections after their poor response to monthly therapy. The short-term use of bi-weekly dosing may be an attractive treatment option for those eyes that show a treatment response within 2 weeks of an injection, but rebound with increased macular fluid after a month. In the future, VEGF Trap-Eye should provide higher trough levels of anti-VEGF binding activity and eliminate the need for bi-weekly dosing in those eyes with VEGF-mediated exudation that appear unresponsive to monthly ranibizumab or bevacizumab.

Source: Stewart MW, Rosenfeld PJ, Penha FM, et al. Pharmacokinetic rationale for dosing every 2 weeks versus 4 weeks with intravitreal ranibizumab, bevacizumab, and aflibercept (vascular endothelial growth factor Trap-Eye). Retina. 2011; Dec. 18 [Epub ahead of print].DOI: doi: 10.1097/IAE.0b013e31822c290f.

Retinal Venular Caliber in the Prediction of Visual Outcomes Following Intravitreal Ranibizumab Injection Treatments for Neovascular AMD

In this prospective cohort study, investigators examined whether baseline retinal vascular caliber predicts visual response to intravitreal ranibizumab injections in patients with neovascular age-related macular degeneration (AMD).

They administered three monthly intravitreal injections of ranibizumab in patients with neovascular AMD and followed that with as-needed dosing for up to 1 year. They also measured retinal vascular caliber from digital fundus photographs at baseline and summarized it as central retinal artery equivalent (CRAE) and venular equivalent (CRVE), representing average caliber of arterioles and venules, respectively. Additionally, the investigators assessed visual outcome at 12 months and determined the relation to baseline retinal vascular caliber.

They analyzed a total of 88 eyes at baseline and after accounting for age, sex, size of choroidal neovascularization and number of injections, they found that patients who deteriorated in visual acuity at 12 months had significantly larger baseline CRVE, 243.10 µm (95% confidence interval [CI], 227.01–259.19), compared with those who were stable, 214.30 µm (95% CI, 205.79–222.81) and those who improved, 215.26 µm (95% CI, 204.69–225.84; p=0.007). Moreover, they noted that baseline CRAE did not differ significantly from eyes whose vision deteriorated, 150.12 µm (95% CI, 138.64–148.63) or gaining vision 142.92 µm (95% CI, 136.71–149.13; p=0.69).

The investigators in this study concluded that in eyes with neovascular AMD treated with intravitreal ranibizumab, larger baseline retinal venular caliber was significantly associated with a poorer response to treatment, possibly reflecting increased disease.

Source: Wickremasinghe SS, Busija L, Guymer RH, et al. Retinal venular caliber predicts visual outcome after intravitreal ranibizumab injection treatments for neovascular AMD. Invest Ophthalmol Vis Sci. 2012;53(1):37–41.

Outcomes with a Free RPE-Choroid Graft in Exudative AMD Patients

To report and analyze long-term best-corrected visual acuity (BCVA) outcomes following a free autologous retinal pigment epithelium (RPE)-choroid graft translocation in patients with exudative age-related macular degeneration (AMD), the authors of this prospective cohort study included 130 consecutive patients (133 eyes) with AMD who underwent RPE-choroid graft translocation between October 2001 and February 2006.

All patients had a subfoveal choroidal neovascular membrane with or without hemorrhage and/or an RPE tear. The authors noted that all were either ineligible for or nonresponsive to photodynamic therapy, the standard treatment at the time of surgery. Data collection included preoperative and postoperative visual acuity measurements, fundus photography, fluorescein and indocyanine green angiography and microperimetry. Postoperative BCVA was the main outcome measure.

The mean preoperative BCVA was 20/250, the authors reported. They also observed that four years after surgery, 15% of the eyes had a BCVA of >20/200, and 5% had a BCVA of ≥20/40. One patient achieved a BCVA of 20/32, which was maintained at 7 years after surgery. Furthermore, complications consisted of proliferative vitreoretinopathy (n=13), recurrent neovascularization (n=13) and hypotony (n=2).

In conclusion, RPE-choroid graft transplantation may maintain macular function for up to 7 years after surgery, with relatively low complication and recurrence rates. Retinal sensitivity, BCVA data, and fixation on the graft suggest that the graft, rather than simply the removal of submacular hemorrhage and/or choroidal neovascular membrane, was responsible for the preservation of macular function. This surgery may be an alternative for patients with AMD who cannot undergo other standard treatment.

Source: van Zeeburg EJ, Maaijwee KJ, Missotten TO, et al. A free retinal pigment epithelium–choroid graft in patients with exudative age-related macular degeneration: results up to 7 years. Am J Ophthalmol. 2012;153(1):120–127.

Treatment of Exudative AMD with a Combination of Ranibizumab and Proton Beam Irradiation

The following study investigated the safety and tolerability of ranibizumab combined with proton beam irradiation in treating exudative age-related macular degeneration (AMD).

In it, six eyes (6 subjects) with exudative AMD (4 newly diagnosed; 2 previous treated with ranibizumab) were treated with 4 monthly ranibizumab and 24 GyE proton beam irradiation (2 fractions, 24 hours apart) and seen monthly thereafter and retreated with ranibizumab for decrease in best-corrected visual acuity of ≥2 lines, new macular hemorrhage or fluid noted on optical coherence tomography.

It was reported that follow-up ranged from 12 months to 36 months (mean, 28 months) and that baseline best-corrected visual acuity (BCVA) ranged from 20/40 to 20/250. Final BCVA ranged from 20/25 to 20/400. No radiation retinopathy was noted in any eye. Calculated radiation distribution dose curves indicate that ≤10% of retina received ≥90% of radiation dose in all eyes. It was noted that two subjects lost ≥3 lines of BCVA during follow up, 1 subject in both eyes from enlarging geographic atrophy and the other from worsening fibrovascular pigment epithelial detachment, which was refractory to multiple ranibizumab treatments before enrollment. Among 4 eyes with newly diagnosed exudative AMD, 3 had no fluid on optical coherence tomography at month 12 without further treatment.

To conclude, no safety concerns were noted after 3 years in eyes with exudative AMD treated with ranibizumab combined with proton beam irradiation in this small pilot study. A larger randomized prospective study is underway to further evaluate this combination therapy.

Source: Park SS, Daftari I, Phillips T, Morse LS. Three-year follow-up of a pilot study of ranibizumab combined with proton beam irradiation as treatment for exudative age-related macular degeneration. Retina. 2011;Dec. 16 [Epub ahead of print]. DOI: 10.1097/IAE.0b013e31822a8d6a.

Link Between High-Risk Disease Loci and Response to Anti-VEGF Treatment for Wet AMD

Investigators sought to examine whether there is an association between known age-related macular degeneration (AMD) genetic risk variants in the CFH, ARMS2 and HTRA1 genes and response to anti-vascular endothelial growth factor (VEGF) (ranibizumab or bevacizumab) treatment for wet AMD. In their patient cohort, they found no statistically significant association between response to anti-VEGF therapy and the genotype in both positive-responder and negative-responder groups.

They performed a retrospective review of 150 patients with documented wet AMD based on clinical examination and fluorescein angiogram. Patients received anti-VEGF therapy with ranibizumab and/or bevacizumab. The investigators genotyped them for the single-nucleotide polymorphism rs1061170, rs10490924, rs3750848, rs3793917, rs11200638 and rs932275 and for the indel del443ins54 spanning the CFH, ARMS2 and HTRA1 genes.

There were 57 patients who were characterized as negative responders to anti-VEGF therapy, and 93 patients who were characterized as positive responders. The study investigators reported that there was no significant difference in mean baseline visual acuity between the groups. They followed negative responders for a mean duration of 24.0 months, and positive responders for a mean duration of 22.0 months. Although the frequency of the at-risk alleles was higher in the positive responders when compared with the negative responder, this did not reach statistical significance. Additionally, the investigators found no significant association between genotype and the number of injections or absolute change in visual acuity in both groups of responders.

Larger studies with more power are necessary to further determine whether a pharmacogenetic association exists between wet AMD and anti-VEGF therapy.

Source: Orlin A, Hadley D, Change W, et al. Association between high-risk disease loci and response to anti-vascular endothelial growth factor treatment for wet age-related macular degeneration. Retina. 2012;32(1):4–9.

Evaluation of Small Molecule Visual Cycle Modulator ACU-4429 on Rod Function

ACU-4429 is a first-in-class small-molecule visual cycle modulator that inhibits the isomerase complex and, in mouse models of retinal degeneration, prevents the accumulation of A2E. In the following study, scientists assessed the tolerability, pharmacokinetics, pharmacodynamics and safety of a single, orally administered dose of ACU-4429 in healthy subjects.

They administered single doses ranging from 2 mg to 75 mg and recorded full-field electroretinograms before and after exposure to full-field bleaching light. They took pharmacokinetics samples at predetermined times. Safety assessments included adverse events, vital signs, clinical laboratory assays, electrocardiograms and ophthalmologic examination.

After 45-minute dark adaptation, the scientists noted that their electroretinographic findings demonstrated a dose-related slowing of the rate of recovery that reached its maximum on Day 2 and returned to baseline by Day 7. They found that mean area under the concentration curve and peak plasma concentration increased proportionally with increasing doses and that median time to peak concentration was 4 hours post dose. Furthermore, mean elimination mean half-life was 4 hours to 6 hours and adverse events were mild and visual in nature (dyschromatopsia and alteration in dark adaptation), transient and resolved without a few days. Adverse event frequency was dose dependent.

Oral administration of ACU-4429 produced a dose-dependent inhibition of the b-wave of the electroretinograms, was well tolerated up to 75 mg and demonstrated linear pharmacokinetics across doses, the scientists concluded.

Source: Kubota R, Boman NL, David R, et al. Safety and effect on rod function of ACU-4429, a novel small molecule visual cycle modulator. Retina. 2012;32(1):183–188.

Relationship Between Drusen Extent and Foveal Choroidal Blood Flow in AMD

With the aim of investigating the relationship between drusen extent and foveolar choroidal blood flow in nonexudative age-related macular degeneration (AMD), researchers determined total drusen area, average druse area and total drusen number using a computer program developed to quantify the extent of manually outlined drusen from fundus photographs of 157 patients (239 eyes) with nonexudative AMD. They also used Laser Doppler flowmetery to assess relative choroidal blood velocity (ChBVel), volume (ChBVol) and flow (ChBFlow) in the center of the fovea.

The study researchers found a significant inverse relationship between total drusen area and ChBVol or ChBFlow. They also noted that for every 1-mm² increase in total drusen area, ChBVol decreased by 0.0061 arbitrary units (p=0.03) and ChBFlow decreased by 0.23 arbitrary units (p=0.049). They also discovered that average druse area was significantly inversely related to ChBVol and ChBFlow and that for every 0.01-mm² increase in average druse area, the ChBVol decreased by 0.0149 arbitrary units (p=0.001) and the ChBFlow decreased by 0.4951 arbitrary units (p=0.003). Adjustment for age weakened the significance, although it remained strong for average druse area versus ChBFlow (p=0.017) and ChBVol (p=0.004). The computer-aided quantification of drusen used in this study showed high intra- and intergrader agreement.

The researchers concluded that in patients with nonexudative AMD, there is an association between increased drusen extent and decreased ChBVol and ChBFlow. This suggests the presence of ischemia and possibly the reason why patients with high-risk drusen are prone to advanced disease.

Source: Berenberg TL, Metelitsina TI, Madow B, et al. The association between drusen extent and foveal choroidal blood flow in age-related macular degeneration. Retina. 2012;32(1):25–31.

Use of Intravitreal Bevacizumab and Ranibizumab in PCV

Korean researchers compared the effectiveness of intravitreal injection of bevacizumab and ranibizumab in patients with treatment-naïve polypoidal choroidal vasculopathy (PCV). They found that intravitreal injections of bevacizumab and ranibizumab have similar effects in stabilization of visual acuity, macular edema and regression of polypoidal complex with PCV eyes.

They retrospectively reviewed a total of 66 and 60 eyes of 121 consecutive patients who received intravitreal bevacizumab (1.25 mg) or ranibizumab (0.5 mg) injection for treatment of PCV. After initial three loading injections by month, they performed injection as needed. Main outcome measured included best-corrected visual acuity (BCVA), foveal center thickness (FCT) as assessed by spectral domain optical coherence tomography (SD-OCT) and change in polypoidal lesion on indocyanine green angiography (ICGA).

According to the researchers, at 12 months, average number of injections was 4.72 ± 1.84 in the bevacizumab group and 5.52 ± 1.54 in the ranibizumab group. They noted that mean logarithm of the minimum angle of resolution of BCVA from baseline at 12 months after injection improved by 0.11 in the bevacizumab group (p=0.02) and by 0.14 in the ranibizumab group (p=0.01). They also reported that average FCT decreased from 368 ± 62.48 to 298 ± 40.77 µm in the bevacizumab group (p=0.01) and from 371 ± 50.79 to 286 ± 36.93 µm in the ranibizumab group (p=0.01). Additionally, polyp regression rate was 24.2% (16 eyes out of 60 eyes) in the ranibizumab group. There was no statistically significant difference in BCVA improvement achieved, FCT improvement achieved and polyp regression rate between groups.

Source: Cho JH, Kim JW, Lee DW, et al. Intravitreal bevacizumab and ranibizumab injections for patients with polypoidal choroidal vasculopathy. Eye. 2011;Dec.16 [Epub ahead of print]. DOI: 10.1038/eye.2011.324.

PDT Plus Intravitreal Ranibizumab for the Treatment of Polypoidal Choroidal Vasculopathy

Japanese investigators conducted the following retrospective chart review to evaluate the 1-year efficacy and safety of photodynamic therapy (PDT) combined with intravitreal injections of ranibizumab for polypoidal choroidal vasculopathy (PCV).

They retrospectively reviewed the medical records of 63 consecutive patients (66 eyes) with subfoveal PCV who were treated with PDT combined with intravitreal injections of ranibizumab. Of the 66 eyes, they found that 29 had no history of treatment for PCV, 10 had been treated previously with only intravitreal injections of anti-vascular endothelial growth factor agents and 27 had been treated previously with PDT. All eyes had a minimal follow up of 12 months.

The investigators noted that the combined therapy reduced substantially the exudative change immediately after initiation of treatment and that in treatment-naïve eyes, mean VA before treatment (0.47 ± 0.37 logarithm of the minimal angle of resolution [logMAR]) improved to 0.32 ± 0.30 (p<.01) at 3 months and to 0.29 ± 0.29 (p<.01) at 12 months. They also observed that polypoidal lesions were reduced in all eyes and disappeared completely in 79.1% of cases. In eyes treated previously with only anti-vascular endothelial growth factor therapy, some visual improvement was achieved, but in eyes treated previously with PDT, mean visual acuity (0.61 ± 0.45) deteriorated to 0.68 ± 0.52 at 12 months. Of all 66 eyes, 5 showed extensive postoperative subretinal hemorrhage, in 2 of which a vitreous hemorrhage developed necessitating pars plana vitrectomy.

In conclusion, PDT combined with ranibizumab led to significant visual recovery in treatment-naïve eyes with PCV, but not in eyes with PCV that had demonstrated recurrence after previous PDT. PDT in combination with ranibizumab still has a risk of the postoperative hemorrhagic complications.

Source: Tomita K, Tsujikawa A, Yamashiro K, et al. Treatment of polypoidal choroidal vasculopathy with photodynamic therapy combined with intravitreal injections of ranibizumab. Am J Ophthalmol. 2012;153(1):68–80.

Visual Function Following Macular Translocation Surgery for Myopic CNV and AMD

Researchers in Japan evaluated the changes in the best-corrected visual acuity (BCVA) after 1 year and after ≥5 years after macular translocation for age-related macular degeneration (AMD) or myopic choroidal neovascularization (mCNV).

They reviewed the medical records of 61 consecutive patients who underwent macular translocation with 360° retinotomy for AMD (35 eyes) or mCNV (26 eyes). Overall, they followed 40 patients, 17 mCNV and 23 AMD, for at least 5 years. BCVA and area of the Goldmann visual field (VF) measured before, 12 months after surgery, and at the final visit.

According to the researchers, in the 23 AMD eyes followed for ≥5 years, the mean preoperative BCVA was 1.149 ± 0.105 logMAR units, which significantly improved to 0.69 ± 0.06 logMAR units at 1 year (p<0.001). They noted that this BCVA was maintained at 0.633 ± 0.083 logMAR units on their final examination. They also found that in the 17 eyes with mCNV followed for ≥5 years, the mean preoperative BCVA was 1.083 ± 0.119 logMAR units, which was significantly improved to 0.689 ± 0.121 logMAR units at 1 year (p=0.001). This BCVA was maintained at 0.678 ± 0.142 logMAR units on their final examination. The study researchers reported that the area of the VF was significantly decreased at 12 months and did not change significantly thereafter.

Their results show that macular translocation surgery significantly improves the BCVA and significantly decreases the VF area of eyes with mCNV or AMD after first 1 year. The BCVA and VF area do not change significantly from the values at 1 year for at least 5 years.

Source: Takeuchi K, Kachi S, Iwata E, et al. Visual function 5 years or more after macular translocation surgery for myopic choroidal neovascularization and age-related macular degeneration. Eye. 2011;Dec. 16 [Epub ahead of print]. DOI: 10.1038/eye.2011.302.

Predictors of Visual Outcome of Epiretinal Membrane Surgery

To evaluate the utility of preoperative optical coherence tomography (OCT) and multifocal electroretinography (mfERG) in prediction of visual outcomes after idiopathic epiretinal membrane (ERM) surgery, the authors of this retrospective, observational case series reviewed 100 eyes of 100 patients with idiopathic unilateral ERM who underwent vitrectomy for ERM removal.

They investigated correlations between preoperative data (OCT and mfERG) and final best-corrected visual acuity (BCVA) using Pearson correlated analysis and used one-way analysis of variance (ANOVA) to determine whether final BCVA and mfERG values differed among subgroups varying in photoreceptor integrity status. The authors also performed receiver operating characteristic (ROC) curve analysis to obtain a cutoff value of the P1 implicit time predicting recovery (final BCVA ≥20/25).

They observed that BCVA significantly improved, and 65 of 84 eyes (77%) achieved visual recovery of more than 2 Snellen lines after ERM surgery. They also reported that final BCVA was significantly correlated with preoperative photoreceptor integrity and P1 implicit time. Furthermore, the area under the ROC (AUROC) curve was statistically significant when P1 implicit time was examined, and the cutoff value for good visual prognosis was 40.81 msec (sensitivity: 72.7%; specificity: 81.3%).

Photoreceptor disruption detected by OCT and P1 implicit time delay on mfERG were significant predictors of poor visual recovery after ERM surgery.

Source: Kim JH, Kim YM, Chung EJ, et al. Structural and functional predictors of visual outcome of epiretinal membrane surgery. Am J Ophthalmol. 2012;153(1):103–110.

Inner Retinal Visual Dysfunction as a Marker of Non-Proliferative DR

Scientists assessed visual acuity in 18 adults with normal retinal health, 23 adults with diabetes and 35 adults with non-proliferative diabetic retinopathy (NPDR) and normal visual acuity to determine the effect of diabetes on inner and outer retinal function in persons with diabetes and no clinically detectable retinopathy or with NPDR.

They used contrast sensitivity and frequency doubling technology (FDT) sensitivity to assess ganglion cell function. They also measured acuity, dark adaptation, light-adapted visual sensitivity and dark-adapted visual sensitivity to evaluate cone and rod photoreceptor visual function. Additionally, they determined the presence and severity of diabetic retinopathy by grading of 7-field stereoscopic fundus photographs using the Early Treatment Diabetic Retinopathy Study grading system.

The study scientists reported that participants with NPDR exhibited impairment of all measured visual functions in comparison with the normal participants. They noted that inner retinal function measured by FDT perimetry was the most impaired visual function for patients with NPDR, with 83% of patients exhibiting clinically significant impairment. Rod photoreceptor function was grossly impaired, with almost half of the patients with NPDR exhibiting significantly impaired dark-adapted visual sensitivity.

Both inner retinal and outer retinal functions exhibited impairment related to NPDR, the scientists found. FDT perimetry and other visual function tests reveal an expanded range of diabetes induced retinal damage even in patients with good visual acuity.

Source: Jackson GR, Scott IU, Quillen DA, et al. Inner retinal visual dysfunction is a sensitive marker of non-proliferative diabetic retinopathy. Br J Ophthalmol. 2011; Dec. 15 [Epub ahead of print]. DOI: 10.1136/bjophthalmol-2011-300467.

A Look at Vitreous Inflammatory Factors and Serous Macular Detachment in BRVO

The investigators in the following study sought to determine whether vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule-1 (sICAM-1) and pigment epithelium-derived factor are associated with serous retinal detachment (SRD) secondary to branch retinal vein occlusion (BRVO). They found that an excessive increase of vascular permeability secondary to upregulation of VEGF and sICAM-1, along with downregulation of pigment epithelium-derived factor, may contribute to the development of SRD in BRVO patients.

The subjects were 44 BRVO patients with macular edema and 16 controls. The study investigators divided patients into 2 groups by optical coherence tomography (OCT) findings, that is, 18 patients with SRD and 26 patients with cystoid macular edema (CME). They then measured the area of capillary nonperfusion with fluorescein angiography and Scion Image software and examined vitreous fluid samples obtained during pars plana vitrectomy by enzyme-linked immunosorbent assay.

What the investigators found was that the incidence of major BRVO was significantly higher in SRD patients (17/18, 94%) than in CME patients (15/26, 58%, p=0.007), while the nonperfused retinal area was significantly larger in SRD patients (p=0.006). They also reported that vitreous fluid levels of VEGF and sICAM-1 showed a significant increase across the 3 groups (control group, CME group and SRD group) (Ptrend <0.001 and Ptrend <0.001, respectively), while the pigment epithelium-derived factor level showed a significant decrease across the 3 groups (Ptrend <0.001).

Source: Noma H, Funatsu H, Mimura T, et al. Vitreous inflammatory factors and serous macular detachment in branch retinal vein occlusion. Retina. 2012;32(1):86–91.

Retinal Detachment and the Fellow Eye

The following study was conducted to characterize the predisposing pathology and clinical features in the fellow eyes of patients recruited as part of the Scottish Retinal Detachment Study.

The Scottish Retinal Detachment Study was a 2-year prospectively recruited population-based epidemiology study that sought to recruit all incident cases of primary rhegmatogenous retinal detachment (RRD) in Scotland.

A total of 1,202 incident cases of primary RRD were recruited in Scotland over a 2-year period and in 94% (1,130) detailed data on the clinical features of fellow eyes with RRD were available. Full-thickness retinal breaks were found in 8.4% (95/1,130) of fellow eyes on presentation and lattice degeneration was present in 14.5% (164/1,130) of fellow eyes. It was noted that 13% (148/1,130) of affected fellow eyes had a best-corrected visual acuity of 6/18 or worse with previous RRD, the second most common cause of poor vision. Overall, 7.3% (88/1,202) of cases had RRD in both eyes; 60% of cases with consecutive bilateral RRD presented before the macula were affected.

In conclusion, rhegmatogenous pathology in the fellow eye represents an important threat to vision. Fellow-eye detachments are more common in pseudophakic individuals and those with a more myopic refractive error. Fellow-eye RRD has a greater likelihood of prompt presentation.

Source: Mitry D, Singh J, Yorston D, et al. The fellow eye in retinal detachment: findings from the Scottish Retinal Detachment Study. Br J Ophthalmol. 2012;96(1):110–113.