Photodynamic therapy with verteporfin for choroidal neovascularisations in clinical routine outside the TAP study. One- and two-year results including juxtafoveal and extrafoveal CNV

Introduction The aim of this study was to analyse 1- and 2-year outcomes after photodynamic therapy (PDT) in clinical routine outside of the TAP [treatment of age-related macular degeneration (AMD) with PDT] study. We analysed the functional results, possible influencing factors and the rate of side effects.Methods We analysed the medical records of 210 consecutive patients between 50 and 93 years of age (73±9 years) who had been treated with PDT for active 50% classic CNV resulting from AMD. Only patients with a minimum follow-up of 1 year (127) were included; 52 patients completed 2 years of follow-up. Juxta- and extrafoveal CNV were also analysed. Treatment was given in accordance with TAP parameters and regular follow-up examinations were performed with standardised ETDRS visual acuity (VA) measurements and fluorescein angiography.Results In the subfoveal group, in 63.6% (70/110) a loss of VA 3 lines could be prevented after 1 year, and in 51.1% (23/45) after 2 years. An improvement of 1 line was found in 31.8% (1 year) and in 22.2% of eyes (2 years). Severe VA loss of 6 lines occurred in 10.9% of cases after 1 year and in 15.6% after 2 years. The mean change of VA was –1.7±3.4 lines (1 year) and –2.5±3.9 lines (2 years). For the group of CNV with juxta-/extrafoveal localisation, the mean change of VA was +0.8±2.5 lines after 1 year and +1.0±4.2 lines after 2 years. With regard to different CNV localisations, the results for juxta-/extrafoveal CNV are statistical significantly better (p=0.005 and p=0.035 after 1 and 2 years, respectively). A mean of 2.6 treatments were performed in the first year and 0.5 in the second year.Conclusions The results obtained in a single institution compare favourably with the results of the TAP study. The results regarding functional visual outcome could be obtained with a lower number of treatments in clinical practice. Juxta- and extrafoveal CNV showed significantly better results than a subfoveal localisation of the CNV. In this subgroup a mean improvement of VA could be obtained after 1 or 2 years.     

A prospective study on intravitreal bevacizumab (Avastin®) for neovascular age‐related macular degeneration of different durations

Purpose: Choroidal neovascularization (CNV) accounts for 85–90% of severe visual impairment in age‐related macular degeneration (AMD). Vascular endothelial growth factor (VEGF) is a major factor mediating angiogenesis, and VEGF inhibitors have become a new treatment modality. In this prospective study, we used bevacizumab (Avastin^®), a recombinant monoclonal antibody to VEGF, to treat neovascular AMD. Methods: The case material comprised 36 subjects (26 females, 10 males) aged 65–88 years with subfoveal neovascular AMD with all subtypes of CNV. There were two categories of patients: category I, long‐standing CNV (12 months or more), preoperative visual acuity (VA) 0.16 (mean); category II, CNV (duration <12 months), preoperative VA 0.25 (mean). Evaluation protocol included the Early Treatment Diabetic Retinopathy Study (ETDRS) VA, clinical ophthalmological examination, fluorescein angiography and optical coherence tomography (OCT). Intravitreal injections of bevacizumab (Avastin^®) (IVB), 1.25 mg (0.05 ml), were given under an operating microscope and aseptic conditions in a theatre for surgery with intervals of 4 or 6 weeks during the first 3 months and subsequently according to clinical assessment. The follow‐up was 6 months in all cases. Results: At 6 months, mean VA had improved by 4.6 ETDRS letters in the entire case material (P = 0.001), by 3.9 letters in category I (duration 12 months or more) and by 6.0 letters in category II (duration <12 months). A total of 148 IVB (mean 4.1 injections/eye) were delivered during 6 months, the first 3 months comprising 3.1 IVB (mean) and the last 3 months 1.0 IVB (mean). No eyes suffered visual decline of 15 ETDRS letters. Fluorescein angiograms displayed stabilization or regression of CNV activity; OCT showed resorption of intraretinal oedema and subretinal fluid. No severe complications occurred but recurrence was common, and repeated IVBs were necessary in most cases during the 6‐month period. Conclusion: When addressing the issue of frequency of IBV, we observed that 6‐week intervals were sufficient because VA and CNV lesions generally stabilized at 4 weeks. The gain in VA was promising in eyes with <12 months CNV duration. Even in eyes with a longer CNV duration, a slight visual improvement was observed when retinal oedema resorbed, although subretinal fibrosis and general cellular damage certainly limited recovery.     

Comparison of visual acuity outcomes between ranibizumab and bevacizumab treatment in neovascular age-related macular degeneration

AIM: To compare visual acuity (VA) outcomes between intravitreal injection of bevacizumab and ranibizumab in the treatment of neovascular age-related macular degeneration (AMD). METHODS: We conducted a consecutive, retrospective case series study in patients with newly diagnosed all type choroidal neovascularization (CNV) secondary to AMD who received an intravitreal injection of bevacizumab (1.25mg) or ranibizumab (0.3mg) at Lions Eye Institute, Western Australia from Mar. 2006 to May 2008. All patients received injection at baseline with additional monthly injections given at the discretion of the treating physician. Main outcome measures were changes in VA. RESULTS: There were 371 consecutive patients received injection at least in one eye with at least 6 months of follow up (median of 12.0 months). Bevacizumab treatment prevented 221 out of 278 (79.5%) patients from losing < 15 letters in VA compared with 79 out of 93 (84.9%) of ranibizumab treated patients (P=0.25). While 68 (24.5%) of bevacizumab treated patients gained ≥15 letters of VA compared with 24 (25.8%) of ranibizumab treated patients (P=0.79). 75.3% and 66.2% patients benefited from ranibizumab and bevacizumab respectively with final VA better than 6/60 (P=0.10). Multivariate analysis showed that pre-treatment VA was negatively associated with benefit outcome. Assignment of injection was not associated with VA outcome of benefit after adjusting the covariate (P=0.857). CONCLUSION: There are no difference in treatment efficacy in terms of VA between bevacizumab and ranibizumab in routine clinical condition.     

Long-term effects of ranibizumab treatment delay in neovascular age-related macular degeneration

Background

Intravitreal injections of ranibizumab are the standard of care for neovascular age-related macular degeneration (AMD). In clinical trials, comparable efficacy has been shown for either monthly injections or as needed injections upon monthly controls. Unlike in trial settings, treatment in clinical routine is often delayed by complex approval procedures of health insurance and limited short-term surgical capacities.

Methods

Eighty-nine patients with neovascular AMD were followed for 12 months. Early treatment diabetic retinopathy study (ETDRS) visual acuity (VA), Radner reading VA and spectral domain optical coherence tomography were performed monthly, with additional fluorescein angiography if needed. After an initial loading phase of three consecutive monthly intravitreal injections with ranibizumab, re-injections were performed when recurrent activity of choroidal neovascularization (CNV) was detected.

Results

After an initial increase to a value of +5.0?±?11.87 ETDRS letters from baseline, VA constantly decreased over 12 months to a value of ?0.66?±?16.82 ETDRS letters below baseline. Central retinal thickness (CRT) decreased from a value of 438.1?±?191.4 μm at baseline to a value of 289.9?±?138.6 μm after initial therapy and stabilized at a value of 322.4?±?199.5 μm. Loss of VA during latency between indication to treat and treatment was significantly greater than re-gain of VA after re-initiation of therapy (?2.2?±?5.0 versus 0.4?±?7.4 letters; p?=?0.046).

Conclusions

Latency between indication to treat and treatment is responsible for irreversible VA deterioration. A successful PRN treatment regimen for neovascular AMD requires immediate access to therapy after indication.     

The Natural History of Juxtafoveal and Subfoveal Choroidal Neovascularization in High Myopia

Background: To assess the natural history of juxtafoveal and subfoveal choroidal neovascularization in eyes with high myopia.Methods: We retrospectively reviewed the charts of 31 patients (31 eyes) with myopia 6 diopters, well-defined juxtafoveal (1–200 m from the foveal center) or subfoveal choroidal neovascularization (CNV) on fluorescein angiography at baseline, no prior laser treatment, age 55 years and presenting visual acuity (VA) 20/200. Initial and final VA were compared with the Wilcoxon signed rank test. Multifactor analysis of variance was used to assess the association between baseline characteristics of the lesion and final VA. Results: Twenty-two patients were females and 9 males with a median age of 44 years (range 14–55). Median diopters spherical equivalent was -11.5 (range -6, -25). Follow-up ranged from 1 to 20 years (median, 3 years). Nine eyes had juxtafoveal CNV and 22 subfoveal involvement. Median final VA (20/100) was significantly worse than median initial VA (20/50)(p = 0.02). A decrease in VA 2 lines occurred in 18 eyes, whereas 8 eyes remained stable and 5 improved (4 juxtafoveal membranes and 1 subfoveal membrane). Of the 9 juxtafoveal CNV, 7 had a final VA 20/40 after a median follow-up of 4 years. By contrast, only 2 of the 22 subfoveal CNV had a final VA 20/40 (median, 20/100) with a median follow-up of 2.5 years. The only factor associated with better final VA was the initial location of CNV (p = 0.0000). Conclusion: This study confirms the poor functional outcome of subfoveal CNV in degenerative myopia with more than 70% of patients having a final VA of 20/100 or less. Juxtafoveal CNV shows a better functional prognosis. These differences should be considered when planning treatment strategies.     

Ranibizumab for predominantly classic neovascular age-related macular degeneration: subgroup analysis of first-year ANCHOR results

PURPOSE: Subgroup data from a pivotal phase 3 study comparing ranibizumab (LUCENTIS) with verteporfin (VISUDYNE) photodynamic therapy (PDT) in patients with predominantly classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) were retrospectively analyzed to identify patient and disease characteristics that may predict visual acuity (VA) treatment outcomes. DESIGN: Retrospective subgroup analysis of 12-month data from the ANCHOR study. METHODS: Univariate analyses were performed to assess VA outcomes across subgroups based on patients' gender and baseline age, VA score, CNV lesion size, CNV lesion type, and duration of neovascular AMD, followed by multivariate analyses to identify predictors of the VA score change from baseline at 12 months. main outcome measures: Proportion of patients losing <15 letters and proportion gaining > or =15 letters from baseline VA; mean change from baseline VA. RESULTS: On average, all subgroups of ranibizumab-treated patients did better than PDT patients for all three VA outcome measures. In the multivariate analysis, lower baseline VA score, smaller baseline CNV lesion size, and younger baseline age were associated with greater gain of letters with ranibizumab treatment and less loss of letters with PDT. CONCLUSIONS: Subgroup analysis of 12-month data from the ANCHOR study showed ranibizumab to be superior to PDT in all subgroups evaluated, and was consistent with the subgroup analysis of 24-month data from the other pivotal phase 3 study of ranibizumab (MARINA) in showing that the most important predictors of VA outcomes were, in decreasing order of impact, the patient's baseline VA score, CNV lesion size, and age.     

Effekt von Bevacizumab auf die Abhebung des retinalen Pigmentepithels bei okkulter choroidaler Neovaskularisation

Purpose

This study aimed to investigate the effect of bevacizumab on pigment epithelial detachment (PED) in occult choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) and to determine predictive factors.

Methods

73 eyes of patients with AMD and PED due to CNV with subretinal and/or intraretinal fluid were assessed. Patients were treated with 1.25 mg of intravitreal bevacizumab.

Results

After 30.6 weeks, the mean visual acuity (VA) increased from 0.53 to 0.49 logMAR (p=0.170). The mean PED height decreased from 354.4 μm to 277.4 μm (p=0.004). Although 53.4% of the eyes showed a reduction in PED, this did not correlate with a significant change in VA. Predictive factors were a high baseline PED and VA <0.32.

Conclusion

Half of the patients showed PED flattening. Especially in patients with distinctive PED, a response to intravitreal bevacizumab may be expected. This therapy can stabilize VA, but PED flattening does not essentially correlate with an increase in VA.     

A systematic review on the effect of bevacizumab in exudative age-related macular degeneration

Aim  To provide evidence for the effect of bevacizumab on visual acuity (VA) and central retinal thickness (CRT) in exudative age-related macular degeneration Methods  A systematic review of all articles of bevacizumab for exudative AMD was conducted. Articles published up to March 2008 were identified in Medline, Embase, the Cochrane Controlled Trials Register and references from included articles. Search terms were “Bevacizumab or Avastin” and “Macula* or ARMD or AMD or intra(-)vitreal or intra(-)vitreous”. Three observers participated in the data retrieval and assignment of the quality scores. Results  A total of 561 articles were retrieved. Three randomised controlled trials (RCT) and 23 before-and-after studies of patients (n = 1,435) who had received bevacizumab were published. Inclusion criteria varied. Lack of masking was the main methodological shortcoming. These RCTs showed that bevacizumab is more effective than PDT. Bevacizumab was given intravenously or as intravitreal injection. The latter was given once, or repeatedly every 4 weeks, and with or without additional injection when a recurrence occurred, mostly based on visual acuity and/or findings from optical coherence tomography. After intravenous administration, the weighted mean change in VA was +12.8 ETDRS letters (range +11 to +14) and the weighted mean change for CRT was −129 μm (range −100 to −202). For the 23 studies with intravitreal injections, the change in VA was +8.6 letters (range +2 to +26) and the change in CRT was −90 μm (range −46 to −190). The incidence of adverse events was low. The change in VA was 2.7 letters higher for studies with a higher quality vs lower quality. Conclusion  Visual acuity improves and central retinal thickness decreases in patients with exudative AMD after bevacizumab. There is no reasonable doubt that this is caused by bevacizumab. It is likely that a randomised controlled trial will show that bevacizumab is equivalent in effect to ranibizumab, which showed a change in ETDRS of +5.9 letters for occult or minimally classic CNV and +9.8 letters for classic CNV after three monthly injections in two large RCTs. The authors had no commercial or proprietary interest.     

Multifocal electroretinography as a predictor of maintenance of vision after photodynamic therapy for neovascular age-related macular degeneration

Purpose To investigate the role of multifocal electroretinography (mfERG) in predicting the outcome of photodynamic therapy (PDT) for neovascular age-related macular degeneration (AMD). Methods Participants underwent refraction protocol VA assessment using the ETDRS logMAR chart at 1 m, Contrast Sensitivity (CS) using the Pelli-Robson chart at 1 m, fundus fluorescein angiography (FA) and mfERGs in response to 19 segments. Response to PDT was binary (1 = the loss of less than 15 letters at 12 months, 0 = the loss of 15 letters or more) and was used as the dependent variable for logistic regression analysis. Results Logistic regression modelling identified mfERG central segment amplitude, lesion size on FA, VA and CS as predictors of outcome (P = 0.05, 0.02, 0.01, 0.03). The model is stable and has excellent discriminability. Conclusion The outcomes of this study are particularly relevant to patients in the UK who are sometimes treated with PDT alone. A larger prospective study would facilitate development of an index to predict outcome of future treatments for AMD.     

Comparison of foveal-sparing with foveal-involving photodynamic therapy for myopic choroidal neovascularization

Purpose

To evaluate the visual outcomes of choroidal neovascularization (CNV) secondary to pathological myopia in eyes treated with photodynamic therapy (PDT), and to determine the effect of lesion location and foveal involvement on visual prognosis.

Methods

Interventional case series of 24 consecutive patients with myopic CNV treated with PDT. The main outcome measure was final LogMAR visual acuity (VA).

Results

Of 24 eyes, the CNV lesion was subfoveal in 11 and extrafoveal in 13. Overall, the mean LogMAR VA at 24 months was 0.72. Extrafoveal CNV lesions achieved significantly better final VA compared with subfoveal CNV (LogMAR 0.45 vs 1.05, P=0.012). Eyes with extrafoveal CNV lesions were subdivided into foveal-sparing PDT (where the PDT laser spot did not involve the foveal center) and foveal-involved PDT (where the PDT laser covered the fovea). At all time points, the group with foveal-sparing PDT had significantly better VA compared with the foveal-involved group. The final LogMAR VA for the foveal-sparing PDT group was 0.26 compared with 1.00 for the foveal-involved PDT group (P=0.003). At 24 months, 77.8% of foveal-sparing PDT cases achieved VA of ≥20/40, compared with 25% of foveal-involved PDT cases and 9.1% of subfoveal CNV lesions (P=0.006).

Conclusion

For patients with myopic CNV, foveal-sparing PDT results in significantly better long-term visual outcomes compared with those with foveal-involved PDT. Foveal-sparing PDT may be of value for treatment of myopic CNV patients who are not suitable for treatment with anti-vascular endothelial growth factor injections.     

EXTEND‐I: safety and efficacy of ranibizumab in Japanese patients with subfoveal choroidal neovascularization secondary to age‐related macular degeneration

Purpose: To evaluate the efficacy and safety of intravitreal ranibizumab for subfoveal choroidal neovascularization (CNV) secondary to age‐related macular degeneration (AMD) in Japanese patients. Methods: This open‐label, multicentre, Phase I/II study enroled patients into Group A (single injection of ranibizumab nonrandomized doses of 0.3 or 0.5 mg followed by 11 monthly injections of the same dose) and Group B (12 monthly injections of ranibizumab randomized to 0.3 or 0.5 mg). The primary efficacy endpoint was the mean change from baseline in best‐corrected visual acuity (BCVA) score at Month 6. Safety was evaluated in all patients who received ranibizumab. Results: Of 88 patients enroled, 12 entered Group A (six per dose) and 76 entered Group B (0.3 mg: n = 35; 0.5 mg: n = 41). Mean change from baseline in BCVA was significantly increased for both doses (Group B) at Month 6 (0.3 mg: +8.1 letters, p = 0.0006; 0.5 mg: +9.0 letters, p < 0.0001) and Month 12 (0.3 mg: +9.5 letters, p = 0.0001; 0.5 mg: +10.5 letters, p < 0.0001). At Month 12, one patient (0.3 mg) and 0 patients (0.5 mg) lost ≥15 letters, while 37.1% (0.3 mg) and 31.7% (0.5 mg) of patients gained ≥15 letters. Ocular serious adverse events (SAEs) of the study eye were reported in 1 and 2 patients in the 0.3‐ and 0.5‐mg groups, respectively. Nonocular SAEs were experienced by 2 and 5 patients in the 0.3‐ and 0.5‐mg groups, respectively. No cases of endophthalmitis were reported. Conclusion: Ranibizumab was effective and well tolerated in Japanese patients with subfoveal CNV secondary to AMD.     

Anti-VEGF-Therapie der exsudativen AMD

Background

The aim of the study was to evaluate possible prognostic and predictive factors (morphologic and functional) of the individual visual gain/decline after anti-VEGF therapy of exudative AMD.

Patients/methods

Best corrected visual acuity (VA), microperimetric sensitivity (RS), retinal thickness (RT) and autofluorescence pattern (AF) were documented in128 patients with exudative AMD.

Results

Eyes with classic choroidal neovascularization (CNV) had the best visual gain but still remained at a lower level. Eyes which initially had the lowest VA had the largest gain and those with good initial VA could maintain this level. There was no correlation between RT and visual outcome. Eyes with initially normal AF had a significantly greater visual gain.

Conclusions

The type of CNV, initial VA, RS and the initial RT were only of limited usefulness, while the initial foveal AF was most important predictive factor. This may indicate that preexisting changes and irreversible damage in the outer retina and/or retinal pigment epithelium are responsible for the resulting VA after therapy.     

Visual acuity and magnification requirement after ranibizumab in patients with wet age-related macular degeneration

BACKGROUND: The purpose of this study was to examine the visual outcome by measuring visual acuity (VA) and magnification requirement (MR) in patients with wet AMD after repeated intravitreal injections of ranibizumab. PATIENTS AND METHODS: A total of 195 eyes were treated with repeated intravitreal injections of ranibizumab "as needed". VA (Snellen chart) and MR (SZB reading chart) at baseline of 114 eyes with occult or minimally classic lesions, 42 eyes with predominantly classic lesions and 39 with retinal angiomatous proliferations (RAP) were compared at 3 and 6 months after beginning of treatment. RESULTS: The whole group of 195 patients with wet AMD (688 intravitreal injections within 6 months) demonstrated a mean improvement of VA of 0.72 lines after 3 months (p < 0.001) and 1.54 lines after 6 months (p < 0.001) and a mean improvement of MR of 0.59 log units after 3 months (p < 0.001) and 0.73 log units after 6 months (p < 0.001). Mean change in VA after 3 and 6 months demonstrated a significant improvement (p < 0.001 to p < 0.05) for eyes with occult CNV (+ 0.8 /+ 1.6 lines) and RAP (+ 1.2 /+ 1.9 lines) whereas mean improvement in VA for classic CNV (+ 0.02 /+ 0.87 lines) did not reach significance compared to baseline. Comparable results were obtained for the mean change of MR after 3 and 6 months for eyes with occult CNV (+ 0.75 log units/+ 0.92 log units). For eyes with RAP mean improvement of MR was + 0.74 log units after 3 months (p < 0.05) and it was not significant with + 0.8 log units after 6 months (p > 0.05). MR did not show a significant change during follow-up for classic CNV. Apart from eyes with classic CNV, in more than 90 % of the eyes both VA and MR remained stable or improved (loss < 3 lines in VA or deterioration of MR of < 3 log units). Although 45 % of the eyes with predominantly classic CNV had received photodynamic therapies with Verteporfin prior to the intravitreal injections with ranibizumab, MR remained stable in 80 % over 6 months. CONCLUSION: With repeated injections of ranibizumab "as needed", VA could be improved as well as MR could be lowered in a majority of patients with wet AMD and therefore reading ability could be optimized. Over 6 months the treatment frequency was lower compared to the monthly administration.     

Changes in reticular pseudodrusen area in eyes that progressed from early to late age-related macular degeneration

Objective

This retrospective cohort study utilized 3 imaging modalities to analyze quantitatively reticular pseudodrusen (RPD) area changes in eyes that progressed from early to late age-related macular degeneration (AMD).

Methods

Subjects with AMD, unilateral choroidal neovascularization (CNV), and early AMD with RPD in the fellow eye (the study eye) were included. The study eyes underwent indocyanine green angiography (ICGA), near-infrared reflectance (NIR-R), and short-wavelength autofluorescence (AF) imaging of the macula at baseline and at follow-up. Study eyes were analyzed for RPD and for the development of late AMD–CNV and/or geographic atrophy (GA). RPD area was measured at baseline and at follow-up as a percentage of the 30-degree field.

Results

During the study period (mean follow-up time 23.5 ± 5.0 months), 12/31 study eyes developed CNV and 4/31 developed GA. In the eyes that developed CNV, there was a statistically significant decrease in mean RPD area over the follow-up period as seen on AF (P < 0.01) and NIR-R (P = 0.01), and the decrease in mean RPD area approached statistical significance on ICGA (P = 0.08).

Conclusion

Using 3 en face imaging techniques, we demonstrate that RPD undergo dynamic spatiotemporal changes in eyes that progress from early AMD to CNV, namely a decrease in the area of lesions detected.

     

A randomized controlled clinical trial on the efficacy of radiation therapy in the control of subfoveal choroidal neovascularization in age-related macular degeneration: radiation versus observation

· Background: The results of several pilot studies concerning radiation therapy for age-related subfoveal choroidal neovascularization (CNV) have been published recently. Although positive treatment results have been described, it is not known whether this therapy alters the natural course of eyes with neovascular age-related macular degeneration (AMD). A randomized controlled clinical trial was conducted in which radiation therapy was compared with observation in patients with subfoveal neovascular AMD. · Methods: Seventy-four patients with a recent drop in central vision due to subfoveal age-related CNV were randomized to either radiation treatment or observation. Patients with either classic, occult or mixed type CNV were included. Eyes in the treatment group received a radiation dose of 24 Gy in four fractions of 6 Gy. Evaluation of data concerning visual acuity (VA) and fluorescein angiography occurred at 3, 6 and 12 months after inclusion. · Results: At 12 months of follow-up 52.2% of the observation group versus 32.0% of the irradiation group had lost 3 or more lines of VA (P=0.03, log rank test). More severe visual decline, 6 lines or more, was observed in 40.9% of the observation versus 8.8% in the irradiation group (P=0.002 using log rank test). At 12 months 39.6% of the observation group and 20.0% of the treatment group had VA of less than 0.1 (P=0.08, log rank test). The size of the CNV membrane doubled in 25.2% of eyes in the observation group versus 20.0% in the treatment group at 12 months (P=0.5, log rank test). No side effects were observed. · Conclusion: Preservation of VA was significantly better in the treatment group compared with the control group at 12 months. Nevertheless we noted a drop in central vision of 3 or more lines in a substantial proportion of the treatment group. Radiation therapy does not prevent visual loss in all patients with age-related subfoveal CNV, and whether the treatment benefit at 12 months will persist has to be awaited. Received: 26 September 1997 Accepted: 11 November 1997     

Makulatranslokation mit 360°-Retinotomie zur Behandlung der exsudativen Makuladegeneration Funktionelle und angiographische Ergebnisse

Background. During surgical extraction of choroidal neovascular membranes (CNV) in age-related macular degeneration (AMD), the defective foveal retinal pigment epithelium (RPE) is removed. Subsequent translocation of the foveal neural retina to adjacent healthy RPE should result in stabilization and possibly improvement of visual acuity. Methods. A prospective case series was carried out using controlled surgery and examination protocols with examinations made at fixed intervals. The surgical procedures combine counterrotation of the globe, phacoemulsification and implantation of a posterior chamber lens, complete vitrectomy, induction of a total retinal detachment, 360° anterior retinotomy, removal of the subfoveal neovascular complex, foveal translocation outside the RPE defect, reattachment of the retina using F6H8, peripheral laser retinopexy and temporary silicone oil tamponade. Patients. Macular translocation surgery was performed on 100 patients between December 1997 and December 1999. All patients had experienced recent visual loss due to exudative AMD and of these, 26 patients had major macular subretinal hemorrhage, 39 patients had occult and 25 patients classic subfoveal choroidal neovascularization. The preoperative findings in the remaining patients included tears in the pigment epithelium (n=4), polypoidal choroidal vasculopathy (n=1), recurrent subfoveal CNV following laser therapy (n=2) and deep retinal vascular anomalous complexes (n=3). Results. A total of 97 patients completed the 12-month examination. Visual acuity increased by 15 or more ETDRS chart letters in 24 patients, remained stable in 42 patients and deteriorated by 15 or more EDTRS chart letters in 34 patients 12 months postoperatively. The silicone oil tamponade was removed in 97 patients, in 10 patients, silicone oil had to be reinjected because of severe complications. A secondary procedure was necessary in 25 patients, primary PVR was observed in 9 eyes, secondary PVR deve-loped in 10 eyes, a macular pucker in 5 eyes and a macular hole in 1 patient. Other postoperative complications included persistent hypotonia, macular edema, IOL dislocation, keratopathy and recurrent CNV (n=3). Conclusions. Macular translocation is a technically demanding operation, which requires a considerable learning curve. Although the procedure has a high rate of surgical and postoperative complications, the functional and anatomical results appear to be promising for selected patients with subfoveal CNV secondary to AMD.     

Ranibizumab for exudative AMD in a clinical setting: differences between 2007 and 2010

Background/purpose

Visual results of ranibizumab given pro re nata in clinical settings depend greatly from the achievement of the monthly follow-up. In 2007, a previous study performed in our tertiary care showed a mean visual gain of only?+?0.7 ETDRS chart letters, probably because of insufficient number of follow-up visits and injections. We report a second retrospective study of patients whose eyes were treated in the same setting, and whose first injection was performed after April 1 2010. The aim was to check if the changes in the management of AMD patients between 2010 and 2007 achieved better visual results.

Method

One hundred and twenty-two patients (125 eyes) with exudative age-related macular degeneration (AMD) were included. Age, gender, side, type of CNV, VA measured on an ETDRS chart at baseline and at 52 ± 6 weeks, the number of IVT performed, and follow-up visits were recorded. The series was compared to our former series of the year 2007. Results are expressed as means?±?standard deviation. Mann–Whitney’s non-parametric test was used to compare the statistical distribution of the parameters measured. Fisher’s exact test was used for 2?×?2 categorical variables, and the chi-square test for others.

Results

In the 2010 series, the mean visual gain was +6.0?±?11.0 l (?35 to?+?34). During this period, the eyes had 5.0?±?1.8 IVT and 7.8?±?1.4 follow-up visits. No correlation was found between the change in VA and gender, type of CNV, age, or the numbers of IVT and visits. There was a reverse correlation between baseline VA and VA changes (r?=??0.413, p?<?0.0001): i.e., the higher the VA at presentation, the smaller the gain. Comparison between 2010 and 2007 showed that in 2010, patients were older (82.2?±?7.0 vs 78.3?±?7.0 y, p?<?0.0001), had a better baseline VA (60.6?±?12.7 vs 56.1?±?14.6 l, p?=?0.0191) and, despite the reverse correlation between change in VA and VA at presentation, visual results were better: +6.0?±?11.0 vs +0.7?±?11.99 l, p?=?0.0003. In 2010, eyes received more injections: 5.0?±?1.8 vs 3.8?±?1.4 in 2007, p?<?0.0001. However, the series did not differ for the number of visits, gender, side or type of CNV.

Conclusions

In 2010, monotherapy with ranibizumab for exudative AMD achieved better visual results than in 2007 in our clinical setting, despite the treatment of older patients with better baseline VA. This is probably due to the greater number of IVT performed. Alternate strategies, such as “inject and extend” or maintenance therapy, may also account for the better visual results.     

Switch of anti-VEGF agents is an option for nonresponders in the treatment of AMD

Background

Although anti-VEGF therapy of exudative AMD with bevacizumab and ranibizumab proved efficacious in the majority of patients, CNV activity does not respond to continued treatment after repeated injections in a considerable amount of patients. These are referred to as nonresponders. A change of the drug to bevacizumab or ranibizumab could possibly offer an alternative option for the treatment of nonresponding exudative AMD.

Methods and materials

A total of 138 nonresponders who switched therapy from bevacizumab to ranibizumab (n=114) or vice versa (n=24) were included in a retrospective study. Visual acuity (VA) and foveal thickness before and after the switch of therapy were compared. By means of linear regression analysis, we analyzed possible prognostic factors associated with a favorable outcome for visual acuity.

Results

Linear regression analysis revealed a statistically significant benefit for nonresponders when treatment was changed to a different anti-VEGF drug (bevacizumab or ranibizumab). VA at the time of the switch was positively correlated with a beneficial development of VA after changing the drug. There was no significant correlation with age, macular thickness, number of injections before the switch, or the development of VA under treatment before the switch. Both patients switching to Avastin and Lucentis benefitted without statistically significant differences.

Conclusions

An exchange of bevacizumab with ranibizumab or vice versa should be considered in nonresponders in the treatment of exudative AMD. Further prognostic factors may help to identify patients who might benefit from a switch. These factors should be investigated in further studies.     

Intravitreal bevacizumab for subfoveal choroidal neovascularization secondary to age-related macular degeneration in an Indian population

Purpose To investigate the 6-month safety profile and clinical outcomes of intravitreal bevacizumab for treating subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Methods We performed a prospective nonrandomized interventional study of 40 consecutive patients (40 eyes) with subfoveal CNV due to AMD. Patients underwent standard ophthalmic examination, optical coherence tomography, and fundus fluorescein angiography. All patients were administered one or more intravitreal injections of bevacizumab (1.25 mg) as primary therapy. Outcomes were also analyzed in subgroups based on lesion type (classic or occult) and lesion size (≤3000 μm or >3000 μm). Results At the 6 months’ follow-up, mean best-corrected visual acuity (BCVA) improved from 20/160 to 20/100 (P = 0.014), and the mean contrast sensitivity improved from 0.38 to 0.62 (P = 0.001). The mean greatest linear diameter and mean central macular thickness significantly decreased from 3.79 mm to 2.4 mm (P = 0.0001) and from 438.5 μm to 363 μm (P = 0.0001), respectively. Visual acuity gain of 15 letters or more was seen in 20% of patients, and the gain was more in the small-lesion subgroup (31.5%) than in the large-lesion subgroup (9.5%). No significant adverse effects were observed. Conclusion Intravitreal bevacizumab is a safe and effective modality for treatment of CNV secondary to AMD. A significant improvement in BCVA with intravitreal bevacizumab was observed for all lesion types.