Choroidal New Vessels Research Articles

Delayed atrophy of the retinal pigment epithelium after submacular surgery.

We report a case of delayed atrophy of the retinal pigment epithelium (RPE) eighteen months after apparently successful excision of submacular choroidal new vessels (CNV) in a patient with age-related macular degeneration (AMD). Submacular surgery for CNV was achieved without visible disturbance of the underlying RPE in an 83 year old man diagnosed with AMD. At the time of surgery the CNV displayed clinical features consistent with lying internal to Bruchs membrane (Type 2 configuration). There was no visible RPE defect at the fovea and vision improved during the subsequent 12 months follow-up. Eighteen months later, however, an atrophic central RPE defect appeared, with a similar shape to the CNV originally excised. This case demonstrates that submacular CNV with Type 2 configuration can occur in AMD and lead to an initially favourable outcome following submacular surgery. Atrophy of the RPE nevertheless did eventually occur and in a pattern consistent with damage during the original operation. It is important to consider results of longer term follow-up when interpreting success rates for surgery in AMD. (Eur J Ophthalmol 2005; 15: 170-2).

CFH Y402H and ARMS2 A69S Polymorphisms and Oral Supplementation with Docosahexaenoic Acid in Neovascular Age-Related Macular Degeneration Patients: The NAT2 Study.

PurposeGenetic susceptibility could be modified by environmental factors and may also influence differential responses to treatments for age-related macular degeneration (AMD). We investigated whether genotype could influence response to docosahexaenoic acid (DHA)-supplementation in the occurrence of choroidal new vessels (CNV).MethodsThe Nutritional AMD Treatment 2 (NAT2) study was a randomized, placebo-controlled, double-blind, parallel, comparative study, including 250 patients aged 55 to 85 years with early lesions of age-related maculopathy, visual acuity better than 0.4 Logarithm of Minimum Angle of Resolution units in the study eye and neovascular AMD in the fellow eye. Patients were randomized at baseline to receive either 3 daily fish-oil capsules, each containing 280 mg DHA, 90 mg EPA and 2 mg Vitamin E, or placebo.ResultsPatients carrying the risk allele (C) for CFH Y402H had no statistically significant increased risk for developing CNV in the study eye (Hazard Ratio (HR)=0.97; 95% Confidence Interval (CI): 0.54-1.76 for heterozygous and HR=1.29; 95%CI: 0.69-2.40 for homozygous). Patients carrying the risk allele (T) for ARMS2 A69S had no statistically significant increased risk for developing CNV in the study eye (HR=1.68; 95%CI: 0.91-3.12) for heterozygous and HR=1.78; 95%CI: 0.90-3.52 for homozygous). A significant interaction was observed between CFH Y402H and DHA-supplementation (p=0.01). We showed a protective effect of DHA-supplementation among homozygous non-risk patients. Among these patients, occurrence of CNV was 38.2% in placebo group versus 16.7% in DHA group (p=0.008).ConclusionsThese results suggest that a genetic predisposition to AMD conferred by the CFH Y402H variant limits the benefit provided by DHA supplementation.Trial RegistrationISRCTN registry 98246501

Vascularized retinal pigment epithelial detachment in age-related macular degeneration: treatment and RPE tear incidence

To review vascularized-pigment epithelial detachment (V-PED) treatment visual outcome, and to assess acute retinal pigment epithelium (RPE) tear incidence. One hundred and thirty-two eyes of 125 consecutive patients with age-related macular degeneration and V-PED were included. Ninety-four eyes (71.2%) were associated with choroidal new vessels (CNV), 38 (28.8%) with retinal angiomatous proliferation (RAP). Patients, treated over a 10-year period with the time-current therapy, received: verteporfin photodynamic therapy (PDT) (group 1, 38 eyes), combined intravitreal triamcinolone acetonide (IVTA) and PDT (group 2, 44 eyes) or intravitreal anti-VEGF injection (bevacizumab or ranibizumab) (group 3, 50 eyes). Mean follow-up was 20.5 months. At month 12, all eyes treated with PDT or with IVTA and PDT showed a mean significant severe visual decrease. Eyes with CNV lost -0.67 and -0.37 logMAR (p < 0.01 and p < 0.01 respectively), and eyes with RAP -0.55 and -0.31 logMAR (p < 0.01 and p = 0.01 respectively). RPE tear occurred in 14 eyes (36.8%) and in six eyes (13.6%) in groups 1 and 2 respectively. Eyes treated with anti-VEGF therapy showed slight mean visual acuity decrease at month 12. Those with CNV had a mean baseline best-corrected visual acuity (BCVA) of 0.36 ± 0.24 logMAR, final of 0.44 ± 0.30 logMAR (-0.08 logMAR, n.s.). In eyes with RAP, mean baseline BCVA was 0.58 ± 0.39 logMAR, final was 0.78 ± 0.47 logMAR (-0.20 logMAR, n.s.). RPE tear occurred in 14 eyes (36.8%). Patients with either V-PED with CNV or a better baseline BCVA showed greater risk of acute RPE tear (p = 0.01 and p = 0.003 respectively). Effective treatment for vascularized PED is still lacking. Until now, only stabilization of the disease has been achieved using anti-VEGF therapy, but the risk of RPE tear can further hamper our expectations. Baseline characteristics are helpful for prognosis, but patients must be informed of the uncertain response. New therapeutic strategies are needed.

Fluorescein angiography: first step for macular degeneration diagnosis

Abstract Purpose To recall that fluorescein angiography (FA) is not only the basis of our knowledge but also mandatory to improve our understanding. Methods Macular disciform lesions have been described and drawed since about 150 years. It is only in 1977 with the advent of fluorescein that the connection with choroidal new vessels (CNV) was performed. The identification of drusen as precursors of CNV was the following stage. With time a number of precursors and clinical forms of macular degeneration were described. Results Currently, the precursors (Age‐Related Maculopathy) are distinguished from the neovasdcular or atrophic complications (Age‐Related Macular Degeneration). The precursors presenting an early hyperfuorescence can be either hard drusen or RPE atrophy distinguished from each other on the late phase of FA.The late hyperfluorescence of soft drusen particularly when confluent requires a careful analysis of the complete FA sequence to ensure the diagnosis. The neovascular stage presents mainly as sub epithelial occult lesions of which the other types develop that display different angiographic behaviours. Specific aspects have been described gradually based on their FA features. The atrophic stage of the disease seems to behave in a stereotyped way but sub goups are presently identified. Conclusion The fluorescein features of the different component of AMD remain the reference for all other more recent imaging technics and helps to understand and differentiate the various aspects of the disease.

Nutritional AMD Treatment Phase I (NAT-1): Feasibility of Oral DHA Supplementation in Age-Related Macular Degeneration

To create a pilot study in order to evaluate the feasibility of a prospective case-control study of oral supplementation with fish oil (docosahexaenoic acid [DHA]; eicosapentaenoic acid [EPA]) in a population with age-related macular degeneration (AMD). A homogeneous group of 38 patients with drusenoid pigment epithelial detachment in one eye (PED) without choroidal new vessels (CNV) was selected. A complete ophthalmologic examination, and a complete profile of fatty acids in serum (S) and in red blood cell membranes (RBCM), were recorded at day 0 and month 6. In group 1, 22 patients were orally supplemented with EPA (720 mg/day) and DHA (480 mg/day) during 6 months. In group 2, 16 patients were followed as controls. Nutritional recommendations on fish consumption were given to both groups. In group 1, after 6 months supplementation we observed a significant blood enrichment in EPA (EPA-S: 2.20 vs 0.79, p<0.0001 and EPA-RBCM: 2.24 vs 0.85, p<0.0001) and in DHA (DHA-S: 2.47 vs 1.56, p<0.0001 and DHA-RBCM: 6.47 vs 4.67, p<0.0001). No change was observed in group 2 despite nutritional recommendations. In this short followup, no evolution to CNV was noted in either of the two groups. Neither side effects nor dropouts were observed in either of the groups. This study supports the feasibility of a long-term double-masked prospective case-control study in an AMD population in order to evaluate a potential benefit from oral supplementation with DHA.

Foveal RPE autofluorescence as a prognostic factor for anti-VEGF therapy in exudative AMD

Autofluorescence (AF) of the retinal pigment epithelium (RPE) are thought to reflect metabolic activity of the RPE cells, which in turn is largely driven by photoreceptor outer segment renewal. In exudative AMD, choroidal new vessels (CNV) may be confined to Bruch's membrane, or transgress the RPE, with consequence loss of photoreceptor cells. It has been suggested that they may be distinguished with autofluorescence imaging. The aim of our study was to analyze the prognostic value of RPE autofluorescence in relationship to the therapeutic outcome of anti-VEGF (vascular endothelial growth factor) therapy in exudative AMD. AF images (Heidelberg Retina Angiograph) were obtained from 95 eyes (95 patients, mean age 77.64 years, 39 male and 56 female) with exudative macular lesions and associated drusen before therapy with intravitreal Bevacizumab (Avastin). Increased, normal, or decreased AF of a central area with diameters of 500 and 1,000 microm around the foveola were distinguished, and compared with the outcome of central vision. As a measure of data reproducibility (inter- and intraobserver variability), the kappa statistics (K > 0.6 "good", K > 0.8 "excellent") and exact agreement in % were calculated. Analysis of AF showed a significant difference in outcome of visual acuity in eyes with changes in AF of the central 500 and 1000 microm (Mann-Whitney test, p500 mum < 0.001, p1,000 microm = 0.02). Comparison of eyes with increased AF to the other eyes also resulted a significant difference in visual acuity at follow-up (p (incr) < 0.001); those with decreased AF had no significant difference to the eyes with normal or increased AF (p (decr) = 0.1733). The RPE-AF of exudative AMD lesions varies greatly. The AF differences probably represent different kinds of metabolism disorders in the RPE. Furthermore, they apparently have a great influence on the chances of anti- vascular endothelial growth factor (VEGF) therapy success; in particular the development of visual acuity is less favorable in eyes with initially increased central AF.

Tomographie par cohérence optique de type Spectral Domain dans la dégénérescence maculaire liée à l’âge: Premiers résultats avec Spectralis HRA-OCT®

Optical coherence tomography (OCT) imaging has become extremely valuable in demonstrating the presence of neurosensory or retinal pigment epithelial elevation or detachment associated with occult choroidal newvessels. This imaging method has recently been improved using the Fourier Transform and is called Spectral Domain-OCT or SD-OCT. The preliminary results using this imaging technique can now be used to analyze the advantages of the technique's sensitivity and acquisition speed.and methods: A consecutive series of 100 AMD patients was examined prospectively and followed with the Spectralis HRA-OCT device (Heidelberg Engineering, Heidelberg, Germany). Each patient underwent a complete ophthalmologic examination, including biomicroscopy, fluorescein and ICG angiographies, and OCT examinations.Different clinical forms of early AMD and advanced ARMD, either atrophic or exudative, can benefit from this new examination. The various changes were registered, mainly at the level of the outer nuclear layer, the outer limiting membrane, and the interface between the inner and outer segments. Intra- or subretinal fluid accumulation and the variations in retinal thickness were precisely analyzed and compared during follow-up using the Tomography Laser Tracking System.The Tomography Laser Tracking System can efficiently evaluate the results of treatment, correlated with the angiographic and functional data, providing great assistance in diagnosis and indications for treatment and retreatment. Quantitative measurements can be taken, not only in the lesion area, but also of their volume (especially for drusen), which may become useful in detecting complications in high-risk patients.

A new approach for visualisation of dye leakage in fluorescein angiography

INTRODUCTION: Fluorescein angiography (FA) is the more common investigation performed for macular diseases.1 Frozen FA pictures are obtained but direct visualisation of the kinetics of FA is possible only once,...

Autologous Transplantation of the Retinal Pigment Epithelium and Choroid in the Treatment of Neovascular Age-Related Macular Degeneration

To assess excision of choroidal new vessels (CNV) combined with autologous transplantation of the equatorial retinal pigment epithelium (RPE) as a means of restoring vision for patients with acute neovascular age-related macular degeneration (AMD). Prospective interventional cohort study. Twelve patients were recruited into an ethics committee approved trial with informed consent between 2004 and 2005. All had <6 months of acute visual loss owing to subfoveal neovascular AMD and were ineligible for photodynamic therapy. Patients underwent submacular removal of CNV through a single retinotomy. A full-thickness patch graft of RPE, Bruch's membrane, and choroid was harvested from the superior equatorial retina and transplanted into the subfoveal space. The graft was flattened under heavy liquid, before silicone oil exchange. Removal of silicone oil and cataract surgery were performed 3 months later. All patients underwent cataract grading, full refraction, optical coherence tomography, fundus autofluorescence, and fluorescein and indocyanine angiography preoperatively and again 6 months postoperatively. Retinal pigment epithelium samples from 3 patients were tested for ex vivo gene transfer using a recombinant lentiviral vector. Six months after surgery, successful transplantation was determined by the presence of a pigmented subfoveal graft showing RPE autofluorescence and choroidal reperfusion. Visual outcome was assessed by subjective refraction and microperimetry of the retina overlying the graft. Successful viable grafts were seen in 11 patients. Three patients had good visual function on the grafts, with mean logarithm of the minimum angle of resolution (logMAR) improving from 0.88 to 0.79 and maintained beyond 1 year. Operative complications occurred in 8 patients, including retinal detachment in 5 patients and hemorrhage affecting the graft in 4 patients. The mean visual acuity over the whole cohort fell from logMAR 0.82 to 1.16. The excised RPE choroid could also be genetically modified outside the eye with a viral vector applied within the time frame of the operation. Autologous RPE transplantation can in principle restore vision in neovascular AMD, but surgical complications remain high. The possibility for ex vivo gene transfer to the free graft of RPE may widen the scope of this procedure to include gene therapy or adjunctive molecular treatments for AMD.

PHOTODYNAMIC THERAPY AND HIGH-DOSE INTRAVITREAL TRIAMCINOLONE TO TREAT EXUDATIVE AGE-RELATED MACULAR DEGENERATION

In Brief Purpose: To evaluate the efficacy of photodynamic therapy with verteporfin (PDT) and high-dose intravitreous triamcinolone acetonide to treat choroidal new vessels (CNVs) associated with age-related macular degeneration (AMD). Methods: In this prospective, consecutive, comparative, nonrandomized, interventional case series, 30 consecutive eyes of 30 patients with subfoveal CNVs associated with AMD were treated with PDT followed by the intravitreal injection of 19.4 ± 2.1 mg /0.1 mL triamcinolone 5 days later. Fifteen eyes had received no previous treatment (group 1), and 15 had been treated previously with PDT alone (group 2). A group of 15 eyes of 15 patients treated with PDT alone, matched for age and CNV composition and size, served as controls. Changes in best-corrected visual acuity (BCVA; logMAR), the number of Snellen lines improved or lost, and the number of PDT sessions were considered as primary outcome indicators. Results: Group 1 improved an average of 0.7 ± 3.7 Snellen lines (range, −5 to 10) (P = 0.62), group 2 lost an average of −0.7 ± 1.5 Snellen lines (range, −5 to 1) (P = 0.08), and the control group lost an average of −2.2 ± 0.4 Snellen lines (range, -9 to 4) (P = 0.06; Wilcoxon signed rank test). The average number of PDT treatments during the 12-month follow-up was 1.6, 1.2, and 2.8 for group 1, group 2, and the control group, respectively. Intraocular pressure rose in 8 (57%) of 14 eyes in group 1 and in 7 (50%) of 14 eyes in group 2. Cataracts developed in 4 eyes (31%) in group 1 and in 4 eyes (33%) in group 2. Conclusion: Combined PDT/intravitreal triamcinolone acetonide as treatment for AMD-associated CNVs was associated with improved final BCVA and reduced the need for retreatment compared with historical controls. Combined Photodynamic therapy followed by intravitreal triamcinolone acetonide injection at high dose (±20 mg) as treatment for AMD-associated CNVs in all lesion types was associated with improved final vision and reduced the need for retreatment rate compared to historical controls.

PHOTODYNAMIC THERAPY AND HIGH-DOSE INTRAVITREAL TRIAMCINOLONE TO TREAT EXUDATIVE AGE-RELATED MACULAR DEGENERATION

To evaluate the efficacy of photodynamic therapy with verteporfin (PDT) and high-dose intravitreous triamcinolone acetonide to treat choroidal new vessels (CNVs) associated with age-related macular degeneration (AMD). In this prospective, consecutive, comparative, nonrandomized, interventional case series, 30 consecutive eyes of 30 patients with subfoveal CNVs associated with AMD were treated with PDT followed by the intravitreal injection of 19.4 +/- 2.1 mg /0.1 mL triamcinolone 5 days later. Fifteen eyes had received no previous treatment (group 1), and 15 had been treated previously with PDT alone (group 2). A group of 15 eyes of 15 patients treated with PDT alone, matched for age and CNV composition and size, served as controls. Changes in best-corrected visual acuity (BCVA; logMAR), the number of Snellen lines improved or lost, and the number of PDT sessions were considered as primary outcome indicators. Group 1 improved an average of 0.7 +/- 3.7 Snellen lines (range, -5 to 10) (P = 0.62), group 2 lost an average of -0.7 +/- 1.5 Snellen lines (range, -5 to 1) (P = 0.08), and the control group lost an average of -2.2 +/- 0.4 Snellen lines (range, -9 to 4) (P = 0.06; Wilcoxon signed rank test). The average number of PDT treatments during the 12-month follow-up was 1.6, 1.2, and 2.8 for group 1, group 2, and the control group, respectively. Intraocular pressure rose in 8 (57%) of 14 eyes in group 1 and in 7 (50%) of 14 eyes in group 2. Cataracts developed in 4 eyes (31%) in group 1 and in 4 eyes (33%) in group 2. Combined PDT/intravitreal triamcinolone acetonide as treatment for AMD-associated CNVs was associated with improved final BCVA and reduced the need for retreatment compared with historical controls.

Long-term Results of Submacular Surgery Combined with Macular Translocation of the Retinal Pigment Epithelium in Neovascular Age-Related Macular Degeneration

To provide long-term (> or =5 years) follow-up data on patients who had previously undergone macular retinal pigment epithelium (RPE) translocation surgery for choroidal new vessels (CNVs) associated with age-related macular degeneration. Retrospective interventional case series. Four of 9 patients who originally underwent surgery and whose results were reported after 2 years of follow-up were reviewed again 5 to 6 years after surgery. All surviving patients from the original trial were contacted, and those who consented to full ocular examination were called in for review. Examination included best-corrected visual acuity (VA), optical coherence tomography (OCT), fundus autofluorescence, fluorescein angiography (FA), and indocyanine green angiography. Long-term success of RPE translocation was assessed by VA, imaging, angiography, and maintenance of overlying foveal fixation. Comparisons were made to the original 2-year follow-up data previously published. Over the long term, VA had declined further in 3 patients and improved slightly in 1 patient. Significantly, all 4 patients had lost foveal fixation and autofluorescence of translocated RPE, which had been present at the original 2-year follow-up assessment. The RPE graft, however, seemed viable when assessed by OCT, FA, and indocyanine green angiography, and no patient had suffered a recurrence of CNVs. In these 4 patients, RPE choroidal grafts had survived in the subfoveal space for at least 5 to 6 years, but rescue of visual function had been transient. The long-term loss of foveal fixation and graft autofluorescence might be explained by chronic photoreceptor apoptosis, initiated by either surgery or the disease process itself. Caution should be applied when drawing firm conclusions from similar studies that provide data after only 2 years' follow-up.

Photodynamic Therapy for Choroidal Neovascularization on Late-onset Fundus Flavimaculatus

To report the features of three consecutive cases of patients affected with late-onset fundus flavimaculatus (FFM) complicated with choroidal new vessels (CNV) and treated with photodynamic therapy (PDT). Retrospective interventional case series. Three unrelated women (70- to 74-year-old) presented with unilateral decrease of central vision. Diagnosis of FFM and unilateral CNV was made after fundus examination and fluorescein angiography (FA). PDT was performed on the basis of FA features. One to three PDTs were needed for the treatment of CNV. At the end of follow-up (15-24 months), no leakage was present and visual acuity was improved in these three cases. Occurrence of CNV is a rare event in FFM. In these three eyes, PDT successfully stopped the progression of CNV and blocked leakage. We suggest considering PDT as a treatment for CNV in patients affected with FFM.

Prise en charge « basse vision » des patients atteints de DMLA avec néovaisseaux choroïdiens rétrofovéaux traités par PDT à la vertéporfine

To demonstrate the rehabilitation benefit and immediate optical magnification and electronic equipment advantage in an age-related macular degeneration population with retrofoveal choroidal new-vessels treated by photodynamic therapy using Visudyne. Sixty seven consecutive patients with retrofoveal choroidal new-vessels treated by Photodynamic Therapy using Visudyne were referred to an orthoptist for low-vision rehabilitation. The criteria investigated for this study were: long distance visual acuity, reading ability, contrast sensitivity, (before treatment and during post-treatment examinations), and fixation localization and optical equipment model. This study showed and studied visual acuity variations, mostly for patients with good visual acuity at inclusion. Contrast sensitivity stayed more or less the same. Retinal fixation was foveolar most of the time (68.7%). Optical or electronic devices for low-vision patients are numerous and video systems were the most currently used among our population. 62.7% des patients had low-vision rehabilitation with optic aids. This study threw light on patient optic aids which must be prescribed according to his needs and difficulties, without delay. This equipment will then be readapted at each stage of the patient evolution. PDT treatment gives an important role to low-vision rehabilitation associated with optic magnification aids.

Delayed Atrophy of the Retinal Pigment Epithelium after Submacular Surgery

We report a case of delayed atrophy of the retinal pigment epithelium (RPE) eighteen months after apparently successful excision of submacular choroidal new vessels (CNV) in a patient with age-related macular degeneration (AMD). Case report. Submacular surgery for CNV was achieved without visible disturbance of the underlying RPE in an 83 year old man diagnosed with AMD. At the time of surgery the CNV displayed clinical features consistent with lying internal to Bruch's membrane (Type 2 configuration). There was no visible RPE defect at the fovea and vision improved during the subsequent 12 months follow-up. Eighteen months later, however, an atrophic central RPE defect appeared, with a similar shape to the CNV originally excised. This case demonstrates that submacular CNV with Type 2 configuration can occur in AMD and lead to an initially favourable outcome following submacular surgery. Atrophy of the RPE nevertheless did eventually occur and in a pattern consistent with damage during the original operation. It is important to consider results of longer term follow-up when interpreting success rates for surgery in AMD.

La surveillance du patient après traitement: Aspects angiographiques des récidives et indications des retraitements

Dynamic phototherapy with intravenous injection of Verteporfin (Visudyne) is a relatively recent therapeutic concept based on a photochemical reaction. Its statistically significant efficacy has been demonstrated in treating choroidal newvessels and age-related macular degeneration. This occlusion is often temporary, thus requiring repeated treatments in persistent cases and/or recurrences. Angiographic monitoring of the patient, over the short or medium term and then later over the long term, will identify these cases. The indications for retreatment are based on very close follow-up with fluorescein angiographic results, and the persistence or reappearance of leakage should be analyzed and clearly distinguished from staining phenomena. Leakage is an essential element and the main diagnostic criterion of recurrence. Associated criteria could be envisaged based on follow-up angiographic examinations at different stages of progression: early, at 4 or 6 weeks (often a good indicator of progression), or at 3 months, currently indispensable. With a relatively stable lesion with no progression or extension, the angiographic examination will make it possible to decide whether a treatment is needed: either retreatment if there is leakage or no treatment if the lesion is fibrous. To assist in therapeutic decisions, a number of arguments must be gathered based on fluorescein angiography but also on indocyanine green angiography (ICG), which will analyze neovascularization, and optical coherence tomography (OCT) examination, which will bring out the presence or absence of fluid at the lesion, as well as functional signs of visual acuity. In difficult cases, the angiographic examination will determine the source of the major decreases in acuity that can be caused by hemorrhages, breaks (which are not necessarily absolute contraindications for retreatment), or acute choroidal ischemia. Fluorescein and IGC angiographic follow-up and OCT examinations will screen and analyze persistence or reperfusion of choroidal neovessels as well as the extension or reappearance of lesions and, on the other hand, the presence or absence of fibrotic staining phenomena and scarring. The changes in central visual acuity and different functional signs are indicators of patient management and therapeutic indications.