Volume 9, Number 11
WELCOME to Review
of Ophthalmology's Retina
Online e-newsletter. Each month, Medical Editor Philip Rosenfeld,
MD, PhD, and our editors provide you with this timely and easily
accessible report to keep you up to date on important information
affecting the care of patients with vitreoretinal disease.
Use of Circularity Index as a Risk Factor for Progression of GA
The authors of the following cohort study aimed to develop a parameter that can assess the relative rate of progression of geographic atrophy (GA) based on the hypothesis that noncircular configuration of the atrophic lesion may be a risk factor for enlargement.
They included the digitized color photographs of 593 eyes with GA from the Age-Related Eye Disease Study (AREDS). They used a novel parameter called the “Geographic Atrophy Circularity Index” (GACI), which was developed on the basis of area and perimeter measurements to categorize the irregularity of the shape of GA. The GACI ranges from 0.0 to 1.0 and is categorized into three groups: 0.25 (very irregular), 0.25 to <0.75 (partly irregular) and ≥0.75 (circular). Growth rate of GA was the main outcome measure.
The study authors noted that the mean growth rate in the three categories was 0.40 (± 0.18), 0.36 (± 0.30) and 0.21 (± 0.22) mm/year, respectively (p<0.001). By adjusting for known confounders, baseline area, duration of GA and configuration, GACI categories were significantly associated with increased growth rate of GA (p<0.001).
The GACI was associated with the progression rate of GA and may be a useful measure for clinical trial eligibility. The association also suggests that enlargement of GA may be related to the extent of the junctional zone of damaged retinal pigment epithelium, which increases with noncircularity for a given GA area.
Source: Domalpally A, Danis RP, White J, et al. Circularity index as a risk factor for progression of geographic atrophy. Ophthalmology. 2013;Oct 25. [Epub ahead of print]. DOI: 10.1016/j.ophtha.2013.07.047.
Nonresponders to Treatment with Antagonists of VEGF in AMD
In Austria, investigators sought to determine the frequency of nonresponders to anti-vascular endothelial growth factor (anti-VEGF) treatment and find possible reasons for their failure to respond.
They reviewed the records of patients treated the first time with either bevacizumab or ranibizumab until the end of 2008. Based on the availability of measurable results and according to prior publications showing the effect of the therapy, they identified loss of three lines of distance acuity, increase of retinal thickness or lesion size as indicators of nonresponders. Two of these three signs had to be present.
The study investigators included 334 eyes of 283 patients; 74.55% received bevacizumab and 25.45% received ranibizumab. Overall, they identified 14.37% of the eyes as nonresponders (14.06% in the bevacizumab group and 15.29% in the ranibizumab group). They also noted that baseline distance acuity and vitreoretinal adhesions were significantly correlated with nonresponders. Correlations with age, gender, lesion type, other morphologic features, and the kind of anti-VEGF agent failed to be significant. Of the nonresponders, 10.4% showed a delayed but good response to anti-VEGF treatment.
The investigators determined that about 15% did not sufficiently respond to anti-VEGF treatment. Vitreoretinal adherences were the only ophthalmologic factor that could be identified to be significantly correlated with insufficient response.
Source: Krebs I, Glittenberg C, Ansari-Shahrezaei S, et al. Non-responders to treatment with antagonists of vascular endothelial growth factor in age-related macular degeneration. Br J Ophthalmol. 2013;97(11):14431446.
Intravitreal Ranibizumab in Phakic vs. Pseudophakic Neovascular AMD Patients with Good Baseline VA
This retrospective, interventional, comparative study examined the efficacy of intravitreal ranibizumab for the treatment of neovascular age-related macular degeneration (AMD) between phakic and pseudophakic eyes with visual acuity ≥ 0.5 Snellen equivalent.
Newly diagnosed neovascular AMD patients with visual acuity of ≥ 0.5 Snellen equivalent were included in the study and patients were divided into two subgroups: phakic and pseudophakic. All patients received three consecutive monthly intravitreal ranibizumab injections, and then, reinjection was performed as needed. Patients were examined monthly, and the data at baseline, at months three, six, nine and 12 were evaluated. The changes in visual acuity, central retinal thickness and the number of injections were compared between the groups.
The study included 96 eyes of 96 patients (56 phakic and 40 pseudophakic). It was reported that mean Snellen visual acuity at baseline, at months three, six, nine and 12 was 0.56 ± 0.09, 0.64 ± 0.15, 0.62 ± 0.21, 0.60 ± 0.22, and 0.61 ± 0.20 for the phakic group; and 0.55 ± 0.08, 0.63 ± 0.14, 0.60 ± 0.13, 0.58 ± 0.14, and 0.59 ± 0.13 for the pseudophakic group, respectively. The change in mean visual acuity and central retinal thickness at the study visits was not statistically significant between the two groups (p>0.05 for all). Mean injection number at month 12 was 4.5 and 4.3 in the phakic and pseudophakic group, respectively (p=0.5).
In conclusion, intravitreal ranibizumab treatment on an as-needed treatment regimen is effective in preserving vision and improving central retinal thickness in both the phakic and pseudophakic group of neovascular AMD patients with good baseline visual acuity.
Source: Ozkaya A, Alkin Z, Yazici A, Demirok A. Comparison of intravitreal ranibizumab in phakic and pseudophakic neovascular age-related macular degeneration patients with good baseline visual acuity. Retina. 2013;Oct 17. [Epub ahead of print]. DOI: 10.1097/IAE.0000000000000024.
Long-Term Stability of VEGF Suppression Time Under Ranibizumab Treatment in AMD
German researchers conducted this nonrandomized, prospective clinical study to determine intra-individual long-term stability of vascular endothelial growth factor (VEGF) suppression time in eyes with neovascular age-related macular degeneration (AMD) treated with ranibizumab.
In this study, they included 83 eyes of 83 patients with neovascular AMD undergoing intravitreal ranibizumab injections. They took aqueous humor specimens (total=859) before each intravitreal ranibizumab injection and measured VEGF A by multiplex bead analysis.
According to the researchers, ranibizumab resulted in complete VEGF suppression within a mean period of 36.4 days (standard deviation ± 6.7 days; range, 26 to 69 days). Intra-individual suppression time was stable within a period of up to three years. Among 859 VEGF measurements, only five (0.58%) deviated from this pattern. Additionally, nonsuppressed VEGF levels did not differ significantly between baseline and recurrence (68.0 pg/mL vs 69.3 pg/mL) and did not correlate with choroidal neovascularization size and lesion type.
Both the long-term stability and the broad range of individual suppression times after ranibizumab injections would allow and justify adjustment of continuous injections individually to achieve permanent VEGF suppression in patients.
Source: Muether PS, Hermann MM, Dröge K, et al. Long-term stability of vascular endothelial growth factor suppression time under ranibizumab treatment in age-related macular degeneration. Am J Ophthalmol. 2013;156(5):989993.
VMA's Affect on Anti-VEGF Treatment for PCV
To evaluate the effect of posterior vitreomacular adhesion (VMA), documented by optical coherence tomography, on the outcome of anti-vascular endothelial growth factor (anti-VEGF) treatment of polypoidal choroidal vasculopathy (PCV), researchers retrospectively reviewed the medical records of 102 patients (104 eyes) with PCV and categorized them according to the presence of posterior VMA into two subgroups: VMA positive (+) group (23 eyes) and VMA negative () group (81 eyes). Best-corrected visual acuity (BCVA) and central macular thickness after anti-VEGF treatment were compared between the two groups at baseline and at one month, three months, six months and 12 months.
At the last follow-up, the researchers noted that the average number of injections was 4.82 ± 1.27 in the VMA (+) group and 4.92 ± 1.45 in the VMA () group. They reported that, after injection, the mean logarithm of the minimum angle of resolution (logMAR) of BCVA improved from 0.81 ± 0.53 (Snellen equivalent, 20/129) to 0.67 ± 0.52 (Snellen equivalent, 20/93) in the VMA (+) group (p=0.01) and from 0.79 ± 0.50 (Snellen equivalent, 20/123) to 0.64 ± 0.58 (Snellen equivalent, 20/91) in the VMA () group (p=0.02). The study researchers also found that average central macular thickness decreased from 354.4 ± 124.5 µm to 249.6 ± 112.5 µm in the VMA (+) group (p=0.01) and from 361.2 ± 140.2 µm to 267.3 ± 103.5 µm in the VMA () group (p=0.01). Polyp regression rate was 21.7% (five eyes of 23 eyes) in the VMA (+) group and 22.2% (18 eyes of 81 eyes) in the VMA () group. There was no statistically significant difference in the best-corrected visual acuity improvement, central macular thickness improvement, and polyp regression rate between the groups.
To conclude, unlike typical age-related macular degeneration, posterior VMA was not associated with a visual outcome after intravitreal anti-VEGF for PCV.
Source: Cho HJ, Baek JS, Lee DW, et al. Effects of vitreomacular adhesion on anti-vascular endothelial growth factor treatment for polypoidal choroidal vasculopathy. Retina. 2013;33(10):21262132.
A Look at Intravitreal Anti-VEGF Therapy for CNV Secondary to Pathological Myopia
A retrospective, non-randomized, multicenter, consecutive, interventional case series study was performed with the intention to report the visual outcome after four-year follow-up in a series of highly myopic eyes with choroidal neovascularization (CNV) treated with anti-vascular endothelial growth factor (anti-VEGF) drugs.
A total of 92 highly myopic eyes with subfoveal CNV were given intravitreal injections of anti-VEGF. The initial protocol (one vs. three injections) was dictated by surgeons' preferences and followed by an as-needed monthly regime. Best-corrected visual acuity (BCVA) was evaluated at baseline and then monthly. The primary aim was to analyze BCVA changes. The effect of age, spherical equivalent (SE) and treating drug were evaluated as secondary objectives.
It was noted that the mean age of the patients was 57 years (SD 14, range 30 to 93) and that the mean number of letters read was 46.1 (SD 16.8, range five to 70) at baseline, 55.5 (SD 18.6, range 10 to 85) at 12 months, 50.1 (SD 20.1, range five to 82) at 24 months, 54.2 (SD 21.9, range two to 85) at 36 months and 53.1 (SD 22.5, range one to 83) at 48 months (p=0.000, initial vs. 12, 24 and 36 months; p=0.01 initial vs. 48 months; Student t test for paired data). The mean total number of intravitreal injections was 4.9 (SD 5.4, range one to 29). SE and treating drug had no influence on the final visual outcome and number of injections required.
In conclusion, intravitreal bevacizumab and ranibizumab are effective therapies and show similar clinical effects in highly myopic CNV. Visual acuity gain is maintained at four-year follow-up.
Source: Ruiz-Moreno J, Arias L, Montero JA, et al. Intravitreal anti-VEGF therapy for choroidal neovascularisation secondary to pathological myopia: 4-year outcome. Br J Ophthalmol. 2013;97(11):14471450.
Choroidal Thickness Following Treatment for Myopic CNV
To evaluate choroidal thickness in highly myopic eyes with choroidal neovascularization (CNV), three or more years after treatment with photodynamic therapy (PDT), intravitreal ranibizumab (IVR) or both (PDT + IVR), scientists reviewed the medical records of patients with high myopia and CNV treated with PDT or IVR in their department.
They assigned eyes meeting the inclusion criteria to one of three groups: PDT, IVR and PDT + IVR. A fourth group, “dry myopic maculopathy,” included the contralateral highly myopic eyes that never developed CNV. All patients underwent a cross-sectional evaluation with best-corrected visual acuity (BCVA), measurement of axial length, color fundus photography and enhanced depth imaging (EDI) with spectral domain optical coherence tomography (SD-OCT).
The scientists included 42 eyes (21 patients): 11 (26.2%) in the PDT group, eight (19.0%) in the IVR group, nine (21.4%) in the PDT + IVR group and 14 (33.3%) in the dry maculopathy group. They reported that subfoveal choroidal thickness showed no significant differences between groups (p>0.05) and they found a positive correlation between BCVA and macular choroidal thickness (r=+0.293, p<0.001). Furthermore, regression analysis showed that age (p<0.001), axial length (p<0.001), sex (p=0.001) and myopic lesions such as tessellated fundus (p=0.046) and patchy atrophy (p=0.008) were predictive of choroidal thickness. Type of treatment was not predictive of choroidal thickness.
To conclude, older age and greater axial length are the major factors associated with macular choroidal thinning in highly myopic eyes submitted to CNV treatment. The type of treatment performed for myopic CNV had no predictive contribution for choroidal thickness.
Source: Farinha CL, Baltar AS, Nunes SG, et al. Choroidal thickness after treatment for myopic choroidal neovascularization. Eur J Ophthalmol. 2013;23(6):887898.
Half-Dose PDT Targeting the Leakage Point on the Fluorescein Angiography in Acute CSC
Investigators in South Korea evaluated the efficacy of half-dose photodynamic therapy (PDT) targeting only the focal leakage point on fluorescein angiography for acute central serous chorioretinopathy (CSC) in this non-randomized, retrospective, comparative, interventional case series.
Ten consecutive eyes with acute CSC underwent PDT and later 11 eyes were observed without treatment. Main outcome measures included achievement of complete resolution of subretinal fluid (SRF), change in best-corrected visual acuity (BCVA) and central retinal sensitivity.
The investigators noted that complete resolution of SRF was achieved in 80.0% and 18.2% of eyes in the PDT group and the observation group at one month (p=0.009), 100% and 27.3% at three months (p=0.001), and 90% and 63.6% at 12 months (p=0.311), respectively. At 12 months, three eyes (27%) in the observation group had a persistent lesion, while no such lesions were observed in the eyes in the PDT group. One eye in each group showed recurrence during the 12-month follow-up period. Visual acuity improved significantly in both groups at each time point, and the differences between groups were not significant. The mean central retinal sensitivity at three months was significantly higher in the PDT group compared with the observation group.
Fluorescein angiography-guided half-dose PDT appears to facilitate faster resolution of SRF in acute CSC without convincing long-term anatomical and functional benefits, the study investigators concluded. This protocol may further enhance the safety of PDT.
Source: Kim KS, Lee WK, Lee SB. Half-dose photodynamic therapy targeting the leakage point on the fluorescein angiography in acute central serous chorioretinopathy: a pilot study. Am J Ophthalmol. 2013;Nov 4 [Epub ahead of print]. DOI: 10.1016/j.ajo.2013.10.013.
Macular Telangiectasia Changes in MPOD
The authors of the following study quantitatively analyzed the distribution of macular pigment (MP) over a period of five years for monitoring progression of macular telangiectasia.
They determined macular pigment concentration (autofluorescence, excitation wavelengths: 488 and 514 nm) at baseline and after five years in 43 eyes of 22 subjects (46 to 80 years; mean, 65.6 years; 10 men) participating in the macular telangiectasia project.
The study authors found that mean MP density at 0.5° declined in the segment (one-eighth of a circle) with the highest MP optical density (0.04 density units [DU]; p=0.015), and also averaged in the two segments that divided segments with detectable MP from those in which MP was no longer detectable (0.04 density units; p=0.0005). In the first segment mentioned, 2° values decreased to a lesser extent and not significantly. The diameter of MP loss expanded horizontally from 2.64 mm to 2.74 mm (p=0.0001) but not vertically. Macular pigment density in the “halo” of peripheral MP at a mean of 5.44° (4.53 to 6.21°) increased (+0.01 DU; p=0.01).
Five years of follow-up resulted in central (0.5°) reduction and peripheral (4.53 to 6.21°) accumulation of MP. A longer period of follow-up may disclose significant changes in paracentral locations. The area of central MP loss expands in particular in a horizontal direction and less vertically. Centrifugal movement of MP during disease may explain these findings.
Source: Zeimer MB, Spital G, Heimes B, et al. Macular telangiectasia-changes in macular pigment optical density during a 5-year follow-up. Retina. 2013;Oct 20. [Epub ahead of print]. DOI: 10.1097/IAE.0000000000000023.
Residual ILM Following ERM Peeling
A prospective, multicenter, observational study of 98 eyes undergoing pars plana vitrectomy and membrane peeling for idiopathic epiretinal membrane (ERM) sought to determine the degree of residual internal limiting membrane (ILM) after idiopathic ERM peeling and the usefulness of staining with brilliant blue G.
All eyes underwent core vitrectomy (20-, 23- or 25-gauge) followed by intravitreal triamcinolone to verify that the posterior hyaloid had been removed. Brilliant blue G (0.2 mL of 0.25 mg/mL) was injected into the vitreous cavity and washed out immediately. The ERM was peeled and then the surgeon observed and recorded the characteristics of the underlying ILM. The posterior pole was restained with brilliant blue G (0.2 mL of 0.25 mg/mL), and the same observations on the characteristics of the ILM were recorded. Peeling of the remaining ILM was performed. The main outcome measured was the status of the ILM after ERM peel. Secondary outcomes included best-corrected visual acuity (BCVA) and central macular thickness at six months postoperatively.
After ERM peel, it was observed that all of the eyes had residual ILM. It was also noted that in 74 eyes, the ILM was present and damaged, whereas in 24 eyes, the ILM was present and undamaged. In 37 eyes, the operating surgeon was unable to determine the status of the ILM before brilliant blue G staining. At six months, the logarithm of the minimum angle of resolution BCVA improved from 0.75 ± 0.39 at baseline to 0.31 ± 0.26 (p<0.0001). Furthermore, the central macular thickness also improved from 460 ± 91 µm at baseline to 297 ± 102 µm (p<0.003).
It was determined that ILM is frequently still present after ERM peeling and that staining with brilliant blue G facilitates its identification.
Source: Carpentier C, Zanolli M, Wu L, et al. Residual internal limiting membrane after epiretinal membrane peeling: results of the Pan-American Collaborative Retina Study Group. Retina. 2013;33(10):20262031.
Incidence, Characteristics, Evolution and Preventive/Risk Factors of ERM Recurrence
In this retrospective study of 440 consecutive patients (440 eyes) who underwent pars plana vitrectomy for epiretinal membrane (ERM), investigators evaluated the incidence, evolution, clinical characteristics, possible risk factors or preventive factors and visual outcomes of ERM recurrence.
They reported that the internal limiting membrane (ILM) was peeled in 266 cases, with the help of indocyanine green in 27 cases and brilliant blue in 45 cases. Cases of symptomatic ERM recurrence were reoperated on.
According to the investigators, the incidence of ERM recurrence was 5% (22/440), and 2% (9/440) of the patients were reoperated on. They also noted that epiretinal membrane recurrence was symptomatic in nine cases (41%) and asymptomatic in 13 cases (59%). ILM peeling was the only factor preventing ERM recurrence (adjusted odds ratio=0.33, p=0.026). The use of staining dyes did not prevent recurrence (adjusted odds ratio=0.35, p=0.338). In the case of ERM reproliferation, the absence of ILM peeling, the existence of ERM on the fellow eye, and poor visual acuity before surgery seemed to be associated with a high risk of symptomatic recurrence and reoperation. The mean duration for follow-up was 3.5 ± 1.7 years.
The study investigators concluded that ILM peeling not only reduces the likelihood of reproliferation of ERM, but also seems to improve the visual prognosis of recurrent ERMs. The use of dyes did not reduce the rate of recurrence compared with when ILM was peeled without dyes.
Source: Sandali O, El Sanharawi M, Basli E, et al. Epiretinal membrane recurrence: incidence, characteristics, evolution, and preventive and risk factors. Retina. 2013;33(10):20322038.
Evaluation of Retinal and Optic Nerve Head Neovascularization with FD-OCT in PDR
Researchers sought to describe the in vivo spatial and morphological vitreoretinal relationships associated with diabetic retinal neovascularization using Fourier-domain optical coherence tomography (FD-OCT).
They conducted a qualitative assessment of the macula, retina and optic disc head FD-OCT (Topcon 3D OCT-1000) imaging of patients with treatment-naïve and laser-treated proliferative diabetic retinopathy (PDR). They examined the morphology and plane of retinal neovascularization at the disc (NVD) and elsewhere in the retina (NVE), and also evaluated the posterior vitreous relationships. The researchers correlated the FD-OCT characteristics of clinical versus subclinical PDR disease with conventional and wide-field Optos fundus fluorescein angiography.
They evaluated 50 eyes of 50 patients in this retrospective study and noted that retinal neovascularization appears as a hyper-reflective complex, with NVE arising from inner retina with disruption through the internal limiting membrane to attach to the posterior hyaloid surface. They also reported that FD-OCT detected subclinical hyper-reflective NVD complexes that were subvisible on color fundus imaging. Moreover, they described retinoschisis, vitreoretinal adhesions and pegs, zones of separation, and intraretinal tractional elements in untreated PDR patients using high-resolution FD-OCT.
FD-OCT can non-invasively characterize retinal and optic nerve head neovascular complexes at different stages of the proliferative disease process. In clinical practice, FD-OCT can monitor the in vivo serial changes of retinal neovascularization over time.
Source: Muqit MM, Stanga PE. Fourier-domain optical coherence tomography evaluation of retinal and optic nerve head neovascularization in proliferative diabetic retinopathy. Br J Ophthalmol. 2013;Oct 24. [Epub ahead of print]. DOI: 10.1136/bjophthalmol-2013-303941.