Lucentis Approved for the Treatment of DME by FDA The FDA has approved Lucentis (ranibizumab injection) for the treatment of diabetic macular edema... First Dry AMD Patient Treated with Higher Dosage of Embryonic Stem Cell-Derived RPE Cells Advanced Cell Technology, Inc. has announced treatment of the fourth patient, the first in the second patient cohort, in its Phase I/II clinical trial for dry AMD... And More...

Affect of Ranibizumab Therapy on Subfoveal Choroidal Thickness in Neovascular AMD

The authors of this Japanese prospective, consecutive, interventional case series sought to investigate the changes in subfoveal choroidal thickness after intravitreal injections of ranibizumab (IVRs) for neovascular age-related macular degeneration (AMD).

They included 80 eyes (40 affected eyes with neovascular AMD and 40 unaffected fellow eyes) of 40 patients. They treated 40 eyes with neovascular AMD with 0.5-mg IVRs monthly for three months and received additional IVRs as needed over the following nine-month period. Additionally, they measured subfoveal choroidal thickness in all 80 eyes by use of enhanced depth imaging optical coherence tomography images before and after starting the IVRs. Changes in subfoveal choroidal thickness after treatment by IVRs over a 12-month period were the main outcome measures.

A total of 23 eyes (57.5%) were diagnosed with typical neovascular AMD, 16 eyes (40%) were diagnosed with polypoidal choroidal vasculopathy, and one eye (2.5%) was diagnosed with retinal angiomatous proliferation, the authors reported. They also noted that 15 eyes (38%) had received some previous treatments for the neovascular lesion before undergoing the IVRs. The mean best-corrected visual acuity of the affected eyes was improved from 0.54 logarithm of the minimum angle of resolution (logMAR) units at baseline to 0.42 at 12 months (p=0.020). The authors reported that the mean subfoveal choroidal thickness in the affected eyes decreased from 244 ± 62 µm at baseline to 234 ± 66 µm at 1 month (p=0.013), 226 ± 68 µm at 3 months (p<0.001), 229 ± 67 µm at 6 months (p=0.002), and 226 ± 66 µm at 12 months (p=0.002; the change ratio, 93%), whereas that in the unaffected eyes changed from 237 ± 80 µm at baseline to 238 ± 83 µm at 12 months (p=0.78). In the affected eyes, they observed that the change ratio of subfoveal choroidal thickness at 12 months was not correlated with the number of IVRs (mean, 5.8 ± 2.9). Furthermore, subfoveal choroidal thickness demonstrated a similar trend toward decreasing during the following period independent of the subtypes of neovascular AMD or the treatment histories.

Subfoveal choroidal thickness decreased after IVRs in eyes with neovascular AMD, the authors found. Intravitreal injections of ranibizuamb may provide a pharmacologic effect not only on the neovascular lesion, but also on the underlying choroid.

Source: Yamazaki T, Koizumi H, Yamagishi T, Kinoshita S. Subfoveal choroidal thickness after ranibizumab therapy for neovascular age-related macular degeneration: 12-month results. Ophthalmology. 2012;119(8):1621–1627.

Use of High-Resolution OCT to Evaluate Subpigment Epithelial Structures in PEDs Secondary to AMD

Investigators in Germany examined eyes with pigment epithelial detachment (PED) for structures underneath the detached retinal pigment epithelium (RPE) cell layer in this retrospective observational case study.

They assessed spectral domain optical coherence tomography (SD-OCT) scans of age-related macular degeneration (AMD)-related PEDs for the presence of distinctive morphological features in the space between the detached RPE and inner Bruch's membrane.

They found that structures were present in the space between the detached RPE and Bruch’s membrane in 14 of 90 eyes with AMD-related PED. The study investigators also noted that each of these eyes showed hyper-reflective material underneath the PED, presenting as highly reflective, multi-layered, laminar structures, usually oriented parallel to Bruch's membrane.

The findings indicate that SD-OCT may be useful for a more refined phenotypic stratification of AMD-associated PED. Further studies are warranted to explore the correlates on other imaging modalities, to investigate the composition of this material and to assess the potential prognostic relevance of this new finding.

Source: Clemens CR, Krohne TU, Issa PC, et al. High-resolution optical coherence tomography of subpigment epithelial structures in patients with pigment epithelium detachment secondary to age-related macular degeneration. Br J Ophthalmol. 2012;96(8):1088–1091.

Predictive Value of Subjective Symptoms and Clinical Signs for the Presence of Treatment-Requiring Exudative AMD

The introduction of vascular endothelial growth factor (VEGF) inhibitors for the treatment of exudative age-related macular degeneration (AMD) has increased the referral rates of AMD patients with visual symptoms to treating centers considerably. However, a large proportion of the referred patients do not qualify for treatment, implying that considerable resources could be saved if these patients could be identified on the basis of the clinical data available in the referring nonspecialized setting.

Researchers in Denmark conducted this prospective observational study of 1,682 consecutive patients referred with suspicion of exudative AMD qualifying for intravitreal angiostatic treatment. They divided patients into two groups on the basis of the structured interviewing about symptoms, ophthalmoscopy, optical coherence tomography scanning, and fluorescein angiography: one qualifying for and another not qualifying for treatment. They used multiple logistic regression to identify independent parameters predicting the need for treatment.

According to the researchers, the presence of metamorphopsia, dyschromatopsia, retinal hemorrhages and exudates, central retinal thickness, and the absence of micropsia were highly significant individual determinants of treatment-requiring AMD. Sudden onset and worsening of symptoms and the presence of a central dark spot covaried with the occurrence of retinal hemorrhages, whereas reduced visual acuity and blurred vision covaried with the presence of both hemorrhages and exudates.

To conclude, patients with treatment-requiring AMD can be reliably identified by questioning about the presence of metamorphopsia and dyschromatopsia and the absence of micropsia, combined with ophthalmoscopical detection of retinal hemorrhages and exudates. This information may improve the triage of patients considered for referral.

Source: Hessellund A, Larsen DA, Bek T. The predictive value of subjective symptoms and clinical signs for the presence of treatment-requiring exudative age-related macular degeneration. Acta Ophthalmol. 2012;90(5):471–475.

VEGF Polymorphisms as Predictors of Treatment Success in Patients with Wet AMD?

There has been general agreement that the central angiogenic regulator vascular endothelial growth factor (VEGF) is an important trigger to the progression of exudative age-related macular degeneration (AMD). The following prospective cohort study tested the hypothesis that VEGF gene polymorphisms play a role in the treatment success with VEGF in patients with exudative AMD.

A total of 185 eyes of 141 patients with exudative AMD who were scheduled for their first treatment with intravitreally administered bevacizumab were included in this trial. All patients were aged >50 years and had angiographically verified exudative AMD. Blood from the finger pad was collected on blood cards for genotyping for the VEGF polymorphisms rs1413711, rs3025039, rs2010963, rs699947, rs3024997, and rs1005230. At each follow-up visit, visual acuity was reassessed and an ophthalmic examination was carried out. Visual acuity outcome, number of retreatments, and overall time of treatment were analyzed in dependence of the VEGF polymorphisms. Mean change in visual acuity at the end of the treatment period was the main outcome measure.

It was noted that the included patients were reinjected with bevacizumab 1 to 15 times, resulting in a total treatment period of 42 to 1,182 days. In univariate analysis, only the G/G genotypes of rs3024997 and rs2010963 compared with all other five single nucleotide polymorphisms (SNPs) showed a significantly lower visual acuity at the end of treatment. In multivariate analysis including parameters such as time, baseline visual acuity, and number of reinjections, none of the SNPs showed a significant correlation.

This study indicates that VEGF polymorphisms are not major predictors of anti-VEGF treatment success in patients with exudative AMD.

Source: Boltz A, Ruiβ M, Jonas JB, et al. Role of vascular endothelial growth factor polymorphisms in the treatment success in patients with wet age-related macular degeneration. Ophthalmology. 2012;119(8):1615–1620.

Establishing a Link Between CFH and ARMS2 Genotypes, Macular Pigment Optical Density, and Neuroretinal Function in Persons Without AMD

Australian scientists sought to determine whether there is a difference in neuroretinal function and in macular pigment optical density between persons with high- and low-risk gene variants for age-related macular degeneration (AMD) and no ophthalmoscopic signs of AMD, and to compare the results on neuroretinal function to patients with manifest early AMD.

They assessed neuroretinal function with the multifocal electroretinogram for 32 participants (22 healthy persons with no AMD and 10 patients with early AMD). They reported that the 22 healthy participants with no AMD had either high- or low-risk genotypes for CFH (rs380390) and/or AMRS2 (rs10490924). The scientists analyzed trough-to-peak response densities and peak-implicit times in five concentric rings. They also assessed macular pigment optical density by use of customized heterochromatic flicker photometry.

Trough-to-peak response densities for concentric rings 1 to 3 were, on average, significantly greater in participants with high-risk genotypes than in participants with low-risk genotypes and in persons with early AMD after correction for age and smoking (p<.05). According to the scientists, the group peak-implicit times for ring 1 were, on average, delayed in the patients with early AMD compared with the participants with high- or low-risk genotypes, although these differences were not significant. Moreover, there was no significant correlation between genotypes and macular pigment optical density.

In conclusion, increased neuroretinal activity in persons who carry high-risk AMD genotypes may be due to genetically determined subclinical inflammatory and/or histological changes in the retina. Neuroretinal function in healthy persons genetically susceptible to AMD may be a useful additional early biomarker (in combination with genetics) of AMD before there is a clinical manifestation.

Source: Feigl B, Morris P, Brown B, Zele AJ. Relationship among CFH and ARMS2 genotypes, macular pigment optical density, and neuroretinal function in persons without age-related macular degeneration. Arch Ophthalmol. 2012;July [Epub ahead of print]. DOI: 10.1001/archophthalmol.2012.1940.

Treatment of RAP with Intravitreal Ranibizumab

In Germany, researchers conducted a retrospective, consecutive case series of 26 eyes (26 patients) treated with intravitreal injections of 0.5 mg ranibizumab for retinal angiomatous proliferation (RAP) to determine the efficacy of the injections in the treatment of RAP in neovascular age-related macular degeneration (AMD). They gave patients intravitreal injections at monthly intervals during upload phase for a three-month period.

The researchers noted that mean visual acuity before treatment was 0.75 ± 0.38 logMAR (mean ± SD, n=26). They also reported that in the upload phase, mean visual acuity improved four weeks after the initial injection to 0.6 ± 0.37 logMAR (n=26) and to 0.53 ± 0.34 logMAR (n=26) four weeks after the third monthly intravitreal injection of ranibizumab. The mean optical coherence tomography (OCT) central foveal thickness reduced from 345 ± 55 µm at baseline to 215 ± 87 µm at three months. In the maintenance phase, mean visual acuity after six months was 0.66 ± 0.38 logMAR (n=12) and 0.7 ± 0.37 logMAR after nine months (n=6). Finally, the mean OCT central foveal thickness was 259 ± 59 (n=13) at six months and 280 ± 127 µm (n=6) at nine-month follow-up.

Intravitreal ranibizumab resulted in an improvement of visual acuity four weeks after the first injection, but was more pronounced after three months, the researchers determined. A reduction in leakage and OCT central foveal thickness was seen three months after the commencement of treatment.

Source: Kramann CA, Schöpfer K, Lorenz K, et al. Intravitreal ranibizumab treatment of retinal angiomatous proliferation. Acta Ophthalmol. 2012;90(5):487–491.

Fluorescein and Indocyanine Green Angiographic Assessment for RAP Diagnosis

To explore the inter-observer agreement in the diagnosis of retinal angiomatous proliferation (RAP) using fluorescein (FA) and indocyanine green angiographies (ICGA) and to detect which morphologic features of the neovascular lesion are associated with RAP diagnosis, scientists conducted a cross-sectional study in which they considered consecutive patients with newly diagnosed neovascular age-related macular degeneration (AMD) evaluated in eight retina centers.

They obtained the FA and ICGA in all centers according to a standard protocol, both performed either as a static or dynamic examination. All images were graded by two observers from different institutions.

The scientists considered 201 eyes with neovascular AMD of 155 consecutive patients (mean age 76 ± 8 years). They reported that overall RAP prevalence was 30% using FA and 26% using ICGA. They also found that patients studied with dynamic angiography were twice as likely to be diagnosed with RAP as those using static angiography. Inter-observer agreement for the overall detection of RAP was high using FA (kappa: 0.868; 95% confidence interval [CI]: 0.793–0.944) and very high using ICGA (kappa: 0.905; 95% CI 0.836–0.974). The study scientists noted that the agreement between the two observers tended to be higher for the truncated vessel than for the anastomosis in FA as well as in ICGA, but no comparison yielded statistical significance (p=0.258 and p=0.584, respectively).

In conclusion, the inter-observer agreement for RAP detection was very good using FA and ICGA, but the overall detection of RAP was higher for dynamic strategy compared with a static strategy.

Source: Parravano M, Pilotto E, Musicco I, et al. Reproducibility of fluorescein and indocyanine green angiographic assessment for RAP diagnosis: a multicenter study. Eur J Ophthalmol. 2012;22(4):598–606.

Role of FAF in PCV

In the following retrospective, observational, consecutive case series, Japanese investigators studied and compared the characteristics of fundus autofluorescence (FAF) in polypoidal choroidal vasculopathy (PCV) with those in typical neovascular age-related macular degeneration (AMD).

Included in the series were 92 patients with PCV (92 affected eyes and 86 unaffected fellow eyes) and 31 patients with typical neovascular occult AMD with no classic choroidal neovascularization (CNV; 31 affected eyes and 24 unaffected fellow eyes). The investigators noted that all study eyes underwent FAF photography with a fundus camera-based system and they evaluated the incidence and distribution of hypoautofluorescence, that is, the manifestation of retinal pigment epithelium (RPE) damages. Main outcome measures were the characteristic FAF findings in PCV.

In the affected eyes with PCV, the sites of the neovascular lesions showed two distinct FAF patterns: 1) the confluent hypoautofluroesence at the polypoidal lesions and 2) the granular hypoautofluorescence at the branching choroidal vascular networks. According to the investigators, the confluent hypoautofluorescence, most of which was surrounded by a hyperautofluorescent ring, was seen in 74 eyes (80.4%) with PCV but was seen in no eyes with typical neovascular AMD (p<0.001). They reported that the granular hypoautofluorescence was seen in 91 eyes (98.9%) with PCV and 27 eyes (87.1%) with typical neovascular AMD (p=0.014). In addition, the eyes with PCV more frequently showed hypoautofluorescence outside the macular area than those with typical neovascular AMD (p=0.021). In the unaffected fellow eyes, the hypoautofluorescence was more frequently observed in patients with PCV than in those with typical neovascular AMD, inside the macular area and in the entire FAF image (p=0.012, p=0.003, respectively).

In eyes with PCV, the polypoidal lesions and the branching choroidal vascular networks appeared to affect the RPE and induce peculiar FAF findings. When compared with the patients with typical neovascular AMD, widespread RPE damage was more frequently observed in the patients with PCV, both in the affected eyes and in the unaffected fellow eyes.

Source: Yamagishi T, Koizumi H, Yamazaki T, Kinoshita S. Fundus autofluorescence in polypoidal choroidal vasculopathy. Ophthalmology. 2012;119(8):1650–1657.

Assessment of Long-Term Results of Intravitreal Bevacizumab for CNV in Pathological Myopia

In an effort to evaluate the long-term results and prognostic factors of intravitreal bevacizumab for myopic choroidal neovascularization (mCNV), the authors of this Italian prospective case series included 32 eyes of 30 patients with mCNV.

They noted that treatment consisted of three monthly 1.25-mg intravitreal bevacizumab injections and compared best-corrected visual acuity (BCVA) and CNV area before and after treatment. Prognostic factors included in the regression analyses were age, axial length, baseline BCVA, pretreatment CNV area, CNV location and peripapillary atrophy area.

The authors evaluated the results at 2 years for 32 eyes and at 3 years for 27 eyes. They reported that mean (±SD) baseline BCVA had improved significantly from 30.1 (±15.6) letters to 45.4 (±13.0) letters at 3 years (p<0.0001), with a better outcome in eyes with juxtafoveal CNV (40.4 ± 13.5 vs. 54.0 ± 5.8, p=0.001). They also found that baseline BCVA correlated positively with final BCVA (β=0.560, p=0.001), while age showed a negative correlation (β=–0.399, p=0.01). Furthermore, CNV area decreased from 0.63 (±0.71) mm² at baseline to 0.40 (±0.57) mm² at 3 years (p<0.0001) and peripapillary atrophy area was the only significant contributing determinant for re-treatment (OR 1.20, 95% CI 1.01 to 1.42, p=0.04).

A regimen of three monthly intravitreal bevacizumab injections yielded effective and sustained results in the treatment of mCNV at 3 years of follow-up, according to the authors. Initial BCVA and age were the factors that correlated independently with BCVA outcome.

Source: Gharbiya M, Cruciani F, Parisi F, Cuozzo G, et al. Long-term results of intravitreal bevacizumab for choroidal neovascularisation in pathological myopia. Br J Ophthalmol. 2012;96(8):1068–1072.

Outcomes of the DA VINCI Study of VEGF Trap-Eye in Eyes with DME at One Year

In this randomized, double-masked, multi-center, phase 2 clinical trial, investigators compared different doses and dosing regimens of Vascular Endothelial Growth Factor (VEGF) Trap-Eye with laser photocoagulation in eyes with diabetic macular edema (DME).

They included diabetic patients (n=221) with center-involved DME and assigned participants randomly to one of five treatment regimens: VEGF Trap-Eye 0.5 mg every four weeks (0.5q4); 2 mg every four weeks (2q4); 2 mg every eight weeks after three initial monthly doses (2q8); or 2 mg dosing as needed after three initial monthly doses (2PRN), or macular laser photocoagulation. The change in best-corrected visual acuity (BCVA) as 24 weeks (the primary end point) and at 52 weeks, proportion of eyes that gained 15 letters or more in Early Treatment of Diabetic Retinopathy Study (ETDRS) BCVA, and mean changes in central retinal thickness (CRT) from baseline.

As previously reported, mean improvements in BCVA in the VEGF Trap-Eye groups at week 24 were 8.6, 11.4, 8.5, and 10.3 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus 2.5 letters for the laser group (p≤0.0085 versus laser). Mean improvements in BCVA in the VEGF Trap-Eye groups at week 52 were 11.0, 13.1, 9.7, and 12.0 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus –1.3 letters for the laser group (p≤0.0001 versus laser), the investigators reported. They also observed that proportions of eyes with gains in BCVA of 15 or more ETDRS letters at week 52 in the VEGF Trap-Eye groups were 40.9%, 45.5%, 23.8%, and 42.2% versus 11.4% for laser (p=0.0031, p=0.0007, p=0.1608, and p=0.0016, respectively, versus laser). Mean reductions in CRT in the VEGF Trap-Eye groups at week 52 were –165.4 µm, –227.4 µm, –187.8 µm, and –180.3 µm versus –58.4 µm for laser (p<0.0001 versus laser). Vascular Endothelial Growth Factor Trap-Eye generally was well tolerated. The study investigators found that the most frequent ocular adverse events with VEGF Trap-Eye were conjunctival hemorrhage, eye pain, ocular hyperemia, and increased intraocular pressure, whereas common systemic adverse events included hypertension, nausea, and congestive heart failure.

They determined that significant gains in BCVA from baseline achieved at week 24 were maintained or improved at week 52 in all VEGF Trap-Eye groups. Vascular Endothelial Growth Factor Trap-Eye warrants further investigation for the treatment of DME.

Source: Do DV, Nguyen QD, Boyer D, et al. One-year outcomes of the DA VINCI study of VEGF Trap-Eye in eyes with diabetic macular edema. Ophthalmology. 2012;119(8):1658–1665.

Relationship Between Homocysteine and Oxidative Stress in Young Adult CRVO

High levels of plasma homocysteine have been reported to be toxic to the vascular endothelium, thereby creating an environment of hypercoagulability and occlusion. Elevated homocysteine has been reported as a risk factor for young adult central retinal vein occlusion (CRVO) cases. The following study aimed to determine whether oxidative stress is an independent risk factor or is homocysteine dependent.

Included were 23 young adult CRVO patients and 54 age- and sex-matched controls. Oxidative stress markers thiobarbituric acid-reacting substance (TBARS), superoxide dismutase (SOD), total thiols, glutathione peroxidase and total antioxidant capacity (TAC) were estimated. Additionally, the effect of homocysteine (25 µm to 200 µm) on cultured bovine retinal endothelial cells (BREC) on oxidative stress parameter TBARS was measured.

A significant increase in the plasma TBARS in CRVO cases compared with controls (p=0.000) was observed and SOD and TAC were significantly lower in CRVO cases than controls (p=0.000, p=0.022). There was a significant negative correlation between TAC and TBARS (p=0.00) and a significant positive correlation between homocysteine and TBARS (p=0.029). Nominal regression analysis showed that TAC and homocysteine influence TBARS significantly and the in vitro study in BREC cells revealed that homocysteine increased the TBARS dose and time dependently.

To conclude, TBARS and homocysteine are known to be independent risk factors for CRVO. TBARS can be influenced by both homocysteine and TAC, thereby contributing to the aetiopathology of CRVO by increasing oxidative stress.

Source: Devi SR, Suganeswari G, Sharma T, et al. Homocysteine induces oxidative stress in young adult central retinal vein occlusion. Br J Ophthalmol. 2012;96(8):1122–1126.

Time-Periodic Characteristics in the Morphology of Idiopathic Central Serous Chorioretionpathy

To investigate the time-period characteristics associated with morphologic changes in idiopathic central serous chorioretinopathy (CSC) using volume scans acquired by spectral-domain optical coherence tomography (SD-OCT), this Korean retrospective, observational, cross-sectional case series involved patients who underwent visual acuity measurement, fundus examinations, fluorescein angiography, indocyanine green angiography, and SD-OCT volume scans.

Patients were classified into five categories: acute CSC, early chronic (EC) CSC, late chronic (LC) CSC, sequelae of CSC, or recurrent CSC according to the chronicity and the recurrence. The relationship between the classification and the detailed morphologic changes of the retinal pigment epithelium and outer retina that were observed in the SD-OCT images was investigated.

A total of 76 eyes from 75 patients were included in this study and serous retinal detachment was relatively higher in acute CSC. Low to flat pigment epithelial detachments (PEDs) were most commonly observed in all stages of CSC, especially in LC CSC, but some semicircular PEDs were occasionally observed in eyes with acute or EC CSC. Retinal dragging with fibrin was most frequently observed in eyes that were in the early stage of acute CSC. A thickened posterior surface of the detached retina was most commonly observed in eyes with acute CSC, whereas a thinned posterior surface of the detached retina was observed in eyes with LC CSC. Hyperreflective dots and subretinal exudates were more commonly observed in eyes with EC and LC CSC than in eyes with acute CSC. Furthermore, in eyes with recurrent CSC, two different patterns of SD-OCT findings were observed; these patterns resembled those that were found in either acute CSC or LC CSC.

It was concluded that SD-OCT patterns in CSC eyes differ according to the chronicity and the recurrence of the disease. Detailed investigation of the retinal pigment epithelium and outer retina using SD-OCT could be useful for estimating the duration of CSC.

Source: Song IS, Shin YU, Lee BR. Time-periodic characteristics in the morphology of idiopathic central serous chorioretinopathy evaluated by volume scan using spectral-domain optical coherence tomography. Am J Ophthalmol. 2012;154(2):366–375.

Surgery Outcome Following Macula-Off Retinal Detachment

Researchers evaluated the anatomical success rate of scleral buckling surgery in the treatment of rhegmatogenous retinal detachment and also evaluated the differences in outcome between patients suffering macula-off retinal detachment and those without a macular involvement.

As a retrospective interventional case series, Munster Study on Therapy Achievements in Retinal Detachment (MUSTARD) is one of the largest ever established of retinal detachment patients and their outcome after buckling surgery, with 4,325 patients who underwent surgery between 1980 and 2001. In 53.94% (n=2134) of 3,956 patients with nontraumatic retinal detachment, the macula was involved. According to the researchers, the main outcome measure was the achievement of dry anatomical attachment of the retina.

They determined that that success rate in patients with macula-off retinal detachment is 80.46% and thus 7.78% lower (p<0.01) than that in those patients with their macula intact whose success rate amounted to 88.24%. They noted that the overall success rate of all 4,325 MUSTARD patients was 83.98%.

Scleral buckling is an established and mostly successful method for the treatment of retinal detachment. As this case series has demonstrated, even eyes with macula-off retinal detachment can be treated successfully by this procedure, thereby avoiding the complications of primary vitrectomy.

Source: Thelen U, Amler S, Osada N, Gerding H. Outcome of surgery after macula-off retinal detachment—results from MUSTARD, one of the largest databases on buckling surgery in Europe. Acta Ophthalmol. 2012;90(5):481–486.