The prevalence of retinal angiomatous proliferation in age-related macular degeneration with occult choroidal neovascularization

Background The purpose of the study was to ascertain the prevalence of retinal angiomatous proliferation (RAP) by means of dynamic indocyanine green angiography (d-ICGA) in patients with newly diagnosed fibrovascular pigment epithelium detachment (type 1) or late leakage of undetermined source (type 2) occult choroidal neovascularization (CNV) on fluorescein angiography. Methods We carried out a review of digital fluorescein and ICG angiograms obtained by confocal scanning laser ophthalmoscope (HRA; Heidelberg Engineering GmbH, Dossenheim, Germany) in 253 consecutive patients (270 eyes) with a clinical diagnosis of type 1 or type 2 occult CNV on fluorescein angiography (1998 through 2003). Results Sixty eyes had type 1 and 210 eyes type 2 occult CNV on fluorescein angiography. Overall, 57 cases of RAP were identified in 54 eyes (20%) with d-ICGA. RAP was present in 6 out of 60 eyes with type 1 (10%) and in 51 out of 210 eyes with type 2 occult CNV (24%). Mean distance of the lesion from the fovea was 682 ± 304 μm (mean ± SD). Conclusions d-ICGA is invaluable for early diagnosis of RAP in exudative age-related macular degeneration (ARMD). In our series, up to one fourth of type 2 occult CNV were in fact RAP. Presented in part at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting, 2004, Fort Lauderdale, Florida, USA.     

Angiographic pattern of recurrent choroidal neovascularization in age-related macular degeneration

PURPOSE: To evaluate the angiographic characteristics of recurrent choroidal neovascularization (R-CNV) in age-related macular degeneration (AMD). METHODS: A prospective investigation on 107 consecutive patients with exudative AMD and CNV not involving the fovea was conducted. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) were planned before krypton laser treatment, and after 3 weeks, 2, 3, 4, 6, 9, 12, 18, and 24 months from photocoagulation. Laser treatment was FA-guided in eyes with classic CNV, and ICGA-guided in eyes with occult CNV on FA. RESULTS: At baseline on FA, 23.3% had classic CNV, whereas, 76.6% showed occult CNV. On ICGA, CNV assumed a focal and a plaque pattern in 81.3 and 18.6% of cases, respectively. Overall, post-laser CNVs occurred in 56 eyes. FA identified well-defined and ill-defined R-CNV in 25 and 75% of cases, respectively. ICGA identified three different R-CNV patterns: focal, annular, and plaque. Focal R-CNV was defined as a single dot-like hyperfluorescence, which was detected in 69.6% of cases, with subfoveal location in half of them. Annular R-CNV was identified by a hyperfluorescent lesion, partially or completely encircling treated area, which was visible in 19.6% of cases, all with subfoveal involvement. Plaque R-CNV was defined as a hyperfluorescent lesion larger than 1 disc diameter in size, and was seen in 10.7% of cases, all with subfoveal location. CONCLUSIONS: ICGA is able to improve R-CNV visualization identifying three different R-CNV patterns. Focal R-CNV is the most frequent pattern and can be re-treated in half of the cases.     

Transpupillary thermotherapy of occult choroidal neovascularization in age-related macular degeneration

Purpose. To evaluate the efficacy of transpupillary thermotherapy (TTT) in management of occult subfoveal choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD). Methods. Retrospective chart review of eyes that were treated with TTT and had at least 12 weeks of follow-up. Base-line and final ETDRS visual acuity and fluorescein angiography (FA) were compared. Results. For the 48 eyes which met inclusion criteria, mean pre-operative visual acuity was 20/128 (range: 20/50–20/500). Average follow-up was 27 weeks (range: 12 weeks–55 weeks). At 3 months after treatment, 12 eyes (25%) improved 2 lines or more, 18 eyes (37.5%) had no change or 1 line of visual improvement, and 18 eyes (37.5%) worsened 1 or more lines. No significant adverse event was noted during treatment. Three eyes developed large submacular hemorrhage within 2 months of treatment. Based on clinical examination and FA, 61% of the eyes appeared to have reduction of subretinal fluid compared to pre-operative evaluations. Conclusion. Visual acuity was stable or improved in 62.5% of eyes in our series and the treatment was well tolerated. Longer follow up and larger number of patients would be required to evaluate the ultimate benefit of TTT in management of occult CNV due to AMD.     

Transpupillary thermotherapy of occult choroidal neovascularization in age-related macular degeneration

PURPOSE: To evaluate the efficacy of transpupillary thermotherapy (TTT) in management of occult subfoveal choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD). METHODS: Retrospective chart review of eyes that were treated with TTT and had at least 12 weeks of follow-up. Base-line and final ETDRS visual acuity and fluorescein angiography (FA) were compared. RESULTS: For the 48 eyes which met inclusion criteria, mean pre-operative visual acuity was 20/128 (range: 20/50-20/500). Average follow-up was 27 weeks (range: 12 weeks-55 weeks). At 3 months after treatment, 12 eyes (25%) improved 2 lines or more, 18 eyes (37.5%) had no change or 1 line of visual improvement, and 18 eyes (37.5%) worsened 1 or more lines. No significant adverse event was noted during treatment. Three eyes developed large submacular hemorrhage within 2 months of treatment. Based on clinical examination and FA, 61% of the eyes appeared to have reduction of subretinal fluid compared to pre-operative evaluations. CONCLUSION: Visual acuity was stable or improved in 62.5% of eyes in our series and the treatment was well tolerated. Longer follow up and larger number of patients would be required to evaluate the ultimate benefit of TTT in management of occult CNV due to AMD.     

Monitoring retinal function during transpupillary thermotherapy for occult choroidal neovascularization in age-related macular degeneration

PURPOSE: To use focal electroretinography to evaluate changes in retinal function during transpupillary thermotherapy (TTT) for neovascular age-related macular degeneration (ARMD). METHODS: Sixteen eyes of 16 patients with ARMD with occult choroidal neovascularization (CNV) were studied. A 630-nm photocoagulator aiming beam was modified for use as a 41-Hz square-wave focal electroretinogram (fERG) stimulus. The stimulus was presented on a light-adapting background by a Goldmann-type lens (visual angle, 18 degrees; mean luminance, 50 cd/m(2)). fERGs were continuously monitored before, during, and after TTT for occult CNV. The amplitude and phase of the fERG's fundamental harmonic were measured. RESULTS: No suprathreshold or adverse clinical events occurred during the course of the study. fERG amplitude decreased transiently during TTT (23% +/- 9% [SE]; P < 0.05). The decrease in amplitude was greatest 16 to 20 seconds and 32 to 40 seconds after the onset of TTT. It was followed by a recovery to baseline amplitude during TTT (48 to 60 seconds after TTT was begun). Within 60 seconds after TTT was completed, fERG amplitude was within the range of baseline. TTT did not alter the fERG phase. Mean fERG amplitudes and phases recorded 1 week and 1 month after TTT were comparable to mean pretreatment levels. CONCLUSIONS: fERG amplitude decreases transiently during TTT, despite the absence of ophthalmoscopically apparent lesions. Intraoperative amplitude depression may result from an adaptation effect to laser light energy and/or hyperthermia, resulting in desensitization of cone photoreceptors and bipolar cells. Treatment sites are electrophysiologically functional 1 month after TTT. Detailed parametric study of a larger patient group is needed to determine whether fERG testing is potentially useful for monitoring and perhaps for controlling and optimizing TTT for choroidal neovascularization.     

Optical coherence tomography identification of occult choroidal neovascularization in age-related macular degeneration

PURPOSE: To evaluate and describe the various optical coherence tomography (OCT) features of occult choroidal neovascularization (CNV) in age-related macular degeneration (AMD) at the time of diagnosis. DESIGN: Prospective, consecutive, observational case series. METHODS: One hundred and fifty-three eyes of 130 consecutive patients with subfoveal occult CNV diagnosed on scanning laser ophthalmoscope (SLO) fluorescein angiography (FA) and SLO indocyanine green angiography (ICGA) were evaluated with OCT. The diagnostic criteria for occult CNV on angiography were heterogeneous hyperfluorescence with late leakage in the macular region associated with pigment epithelial detachment (PED), stippled hyperfluorescent dots, and signs of deterioration. OCT findings were evaluated and described. RESULTS: A PED was observed on OCT in 98% (150 eyes) either as a limited retinal pigment epithelium (RPE) elevation (54 eyes [35.3%]) or a complete detachment (96 eyes [62.7%]). Occult CNV corresponded to zones of hyperreflectivity in contact with the RPE band and was detected in 62.7% of eyes. In fibrovascular PED (63 eyes [65.5%]), the elevated RPE was highlighted posteriorly by a moderately reflective band overlying a hyporeflective cavity. In serous PED, the cavity remained optically empty. The RPE in the detached zone showed changes such as fragmentation (137 eyes [89.5%]). OCT also showed intraretinal (122 eyes [79.7%]) and subretinal (64 eyes [41.8%]) fluid. CONCLUSIONS: Analysis of the various OCT features observed in this study confirms the polymorphic nature of occult CNV in AMD, their exudative reactions, the almost constant presence of PED, and the different changes in the RPE band. OCT examination, therefore, provides valuable data to confirm the features of subepithelial occult CNV.     

Transpupillary thermotherapy of occult subfoveal choroidal neovascularization in patients with age-related macular degeneration.

OBJECTIVE: To evaluate the efficacy of transpupillary thermotherapy for the treatment of occult subfoveal choroidal neovascularization (CNV) in patients with age-related macular degeneration. DESIGN: A retrospective, noncomparative case series. PARTICIPANTS: Sixteen eyes of 15 consecutive patients who presented with occult subfoveal choroidal neovascularization secondary to age-related macular degeneration. INTERVENTION: After informed consent was obtained, 16 eyes of 15 patients were treated with transpupillary thermotherapy. All patients underwent pretreatment fluorescein angiography and were deemed untreatable by the Macular Photocoagulation Study standard. Transpupillary thermotherapy was delivered using a diode laser at 810 nm. A variable spot size of 1.2 mm, 2.0 mm, or 3.0 mm was used depending on the size of CNV. The diode laser was delivered through a contact lens, and treatment was initiated in one spot for 60 seconds' duration at a power range between 360 and 1000 mW. The end point was an area of no visible color change to a light-gray appearance. MAIN OUTCOME MEASURES: In all eyes, outcome was assessed by Snellen chart visual acuity and clinical examination. In 10 of 16 eyes, preoperative and postoperative fluorescein angiography and optical coherence tomography were available. In the remaining 6 of 16 eyes, exudation was measured by postoperative clinical examination alone. RESULTS: Three eyes (19%) showed a two-or-more-line improvement in visual acuity over a period of 6 to 25 months. Mean follow-up was 13 months. Visual acuity remained stable (no change or one-line improvement) in nine treated eyes (56%). The remaining four eyes (25%) showed a decline (equal to one-line worsening or greater) in visual acuity. Fifteen eyes (94%) demonstrated decreased exudation on fluorescein angiography, optical coherence tomography, and/or clinical examination. CONCLUSIONS: Transpupillary thermotherapy shows no deleterious side effects in treating occult subfoveal choroidal neovascularization. A randomized, prospective study is necessary to evaluate treatment efficacy.     

Intravitreal bevacizumab (Avastin) for occult choroidal neovascularization in age-related macular degeneration

Background The purpose of the study is to report data on short-term safety of intravitreal bevacizumab treatment and its effect on visual function, central retinal thickness, and angiographical changes of occult choroidal neovascularization due to age-related macular degeneration. Methods A consecutive interventional case series of 30 patients with active subfoveal occult choroidal neovascularization secondary to age-related macular degeneration was followed after one intravitreal injection of 1.25 mg bevacizumab at baseline and subsequent injections following standardized criteria. At baseline and follow-up visits patients had visual acuity assessment, intraocular pressure measurement, fluorescein angiography, and optical coherence tomography imaging. Results No serious ocular or systemic adverse events were identified. A significant increase of intraocular pressure or signs of retinal toxicity or endophthalmitis were not detected in any patient. Optical coherence tomography revealed significant decrease (p < 0.001) in central retinal thickness after 1 week, 4 weeks, and 12 weeks, respectively. Fluorescein leakage decreased within 1 week and improvement was maintained at week 12 in the majority of patients. Visual acuity improved or remained stable in 29 of 30 patients; improvement of 3 or more lines was seen in 14 of 30 patients; one patients showed improvement of 6 lines. No patient had severe vision loss of 6 lines or more; moderate vision loss of 3 lines was seen in one patient. Re-injections of bevacizumab according to standard criteria were performed one to two times during the follow-up period of 12 weeks with a re-injection interval of 4 to 18 weeks (median 8 weeks). Conclusions Short-term results suggest that intravitreal injection of bevacizumab is well tolerated and for the majority of patients with occult choroidal neovascularization in AMD results in improvement of visual acuity, decrease in central retina thickness, and reduction of angiographic leakage of the lesion. Bevacizumab as intravitreal treatment may provide a novel therapeutic option for selected patients with exudative AMD. Randomized prospective multicenter trials seem justified to further evaluate long term effects and impact of intravitreal bevacizumab on different subtypes of AMD compared to established therapies.     

Indocyanine green angiography-guided laser photocoagulation for occult choroidal neovascularization in age-related macular degeneration

Resolution of exudative manife stations and changes in vision were compared in patients who had indocyanine green angiography-guided laser photocoagulation versus those who had no laser. A retrospective, nonrandomized study was conducted in 176 patients who had laser photocoagulation therapy for occult choroidal neovascularization in age-related macular degeneration. Forty-three percent of 93 treated patients had complete resolution of exudative manifestations and 29% obtained better vision, versus 13% and 11%, respectively, for patients without laser treatment. Presented at the 103rd Annual Meeting of the American Academy of Ophthalmology, a joint meeting with the XXII Congress of the Pan-American Association of Ophthalmology, October 24, 1999, Orlando, Fla.     

Foveolar choroidal circulation and choroidal neovascularization in age-related macular degeneration

PURPOSE: To investigate in a longitudinal study whether foveolar choroidal blood flow changes are associated with the development of choroidal neovascularization (CNV) in AMD. METHODS: Relative foveolar choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBFlow) were assessed in 135 patients with AMD, at baseline and then annually with laser Doppler flowmetry. All study eyes had visual acuity of 20/40 or better and no CNV at the time of enrollment. Comparison of foveolar choroidal circulatory measurements at baseline and their change before the development of CNV was made between eyes that had CNV and those that did not. RESULTS: CNV developed in 28 eyes during the study. Baseline average foveolar ChBVol and ChBFlow in these eyes were 24% (P < 0.0001) and 20% (P = 0.0007) lower than that observed in the 165 eyes in which CNV did not develop. In the eyes with CNV, foveolar ChBVol and ChBFlow decreased by 9.6% and 11.5% before the formation of CNV, whereas in the eyes that did not, they increased by 6.7% (P = 0.006) and 2.8% (P = 0.004), respectively. Eyes with lower baseline foveolar ChBFlow were more likely (risk ratio = 3.47, 95% CI: 1.24-8.70) to show visual loss of three or more lines than were eyes with a higher baseline ChBFlow (P = 0.005). CONCLUSIONS: The development of CNV and visual loss are associated with lower choroidal circulatory parameters at baseline. In addition, the results suggest that decreases in the foveolar choroidal circulation precede the development of CNV in AMD and may play some role in its development.     

Transpupillary thermotherapy of predominantly occult choroidal neovascularization in age-related macular degeneration with 12 months follow-up

PURPOSE: To perform a phase I/II safety and efficacy study in order to assess the outcome following transpupillary thermotherapy (TTT) for occult choroidal neovascularization (CNV) with no or minimally classic CNV in age-related macular degeneration. METHODS: The study comprised 113 referred patients (79 females, 34 males) aged 59-89 years (mean 77.7 years) with predominantly occult CNV. There were 49 cases of occult with no classic CNV and 64 of occult with minimally classic CNV. According to their greatest linear dimension, lesions were classified as being < 3.0 mm or > 3.0 mm. Transpupillary thermotherapy was delivered with a diode laser, emission at 810 nm, duration 60 seconds, laser power 500-800 mW. Clinical examination, ETDRS logMAR visual acuity and fluorescein angiography were carried out at baseline, and at 3, 6 and 12 months in all cases. RESULTS: The average baseline visual acuity was 0.20 (50.6 letters). Following TTT, it was 0.12 (42.0 letters) at 6 months and 0.12 (38.0 letters) at 12 months. Visual acuity improved in 9/113 eyes (8.0%), remained unchanged in 46 (40.7%) eyes, and deteriorated in 58 (51.3%) eyes. There was no significant difference in the proportion of eyes that had lost at least 15 letters at 12 months in the subgroup of occult with no classic CNV (18/49; 36.7%) versus those with minimally classic lesions < 3.0 mm (15/39; 38.5%). However, 13/25 (52.0%) of cases with minimally classic lesions > 3.0 mm had lost at least 15 letters at 12 months (p = 0.31). The most common complications in the 46 eyes that suffered visual loss comprised subretinal progressive fibrosis (18 eyes) and atrophy of the retinal pigment epithelium (13 eyes). CONCLUSIONS: This study shows that TTT generally prevents moderate and severe visual loss at 12 months follow-up in occult CNV with no classic CNV. Eyes with minimally classic lesions with a greatest linear dimension of < 3.0 mm also show the same positive outcome. These results compare favourably with published data on the natural course of the disease. However, minimally classic lesions of > 3.0 mm responded poorly in this treatment setting.     

New occult choroidal vessels in age-related macular degeneration

We studied the clinical characteristics and the natural course of occult choroidal new vessels (CNV) in 78 eyes with age-related macular degeneration (AMD). Cases were included in 2 groups characterized respectively by ill-defined subretinal ooze (group 1) and serous detachment of the retinal pigment epithelium (RPE) with adjacent areas of mottled pigmentation (group 2). Both these forms of occult CNV showed to have a slower evolution compared to the classic CNV occurring in AMD, but they also led to disciform scar and severe visual loss. Occult CNV of group 2, contrary to those of group 1, were often multifocal and extrafoveal. They had a greater tendency to hemorrhages and a faster and less gradual progression to fibrovascular scarring and visual loss. Fluorescein angiography showed choroidal filling delay in the macular region of 47% of eyes of group 1. A perfusion defect of the macular choroid could be the basis of the low perfusion pressure and the consequent low activity of CNV with the angiographic pattern of ill-defined ooze.     

Angiographic characteristics in patients undergoing macular translocation for subfoveal choroidal neovascularization secondary to age-related macular degeneration

PURPOSE: To review in a standardized fashion pre- and postoperative fluorescein angiographic characteristics in patients undergoing limited macular translocation (LMT) with scleral imbrication to treat subfoveal choroidal neovascularization (SFCNV) secondary to age-related macular degeneration (AMD). The current study was undertaken to assess any potential effects of the translocation procedure on altering the angiographic characteristics of SFCNV before laser photocoagulation. METHODS: A consecutive series of patients undergoing LMT for AMD was identified retrospectively. The pre- and postoperative fluorescein angiograms were reviewed in a masked fashion. Angiographic characteristics evaluated included pre- and postoperative lesion components, stability of lesion, and the amount of retinal translocation obtained. RESULTS: Eighty-eight patients (90 eyes) had angiograms of adequate quality to permit evaluation. Time between the preoperative and the prelaser angiogram ranged from 2 to 84 days (median 7.5 days). Neovascular complexes remained unchanged or decreased in size in 79% of patients. There was no statistically significant difference in lesion size between the pre- and postoperative periods (P = 0.34). Retinal movement ranged from 160 microm to 3,320 microm (median 960 microm), with 61% of cases undergoing effective translocation (i.e., the fovea was moved away from the neovascular complex). None of the lesion components or demographic factors evaluated affected the amount of translocation obtained. Larger lesions were more likely to remain subfoveal following translocation (P = 0.004). CONCLUSION: The size and lesion characteristics appear relatively stable following translocation. Amount of retinal movement is not associated with angiographic lesion characteristics. Only size was associated with achievement of desired translocation in the final model, with large lesions being less likely to achieve desired translocation. In our study group, the amount of retinal translocation was variable with 61% of cases undergoing effective translocation.     

Intravitreal bevacizumab for refractory pigment epithelial detachment with occult choroidal neovascularization in age-related macular degeneration

PURPOSE: New medications targeting vascular endothelial growth factor show promise in the treatment of wet macular degeneration. This study describes the clinical response and optical coherence tomography (OCT) findings for patients with refractory pigment epithelial detachment (PED) and occult choroidal neovascular membranes (CNVMs) who were treated with intravitreal bevacizumab. METHODS: A retrospective analysis of data for 10 patients with fibrovascular PEDs, initially treated with intravitreal pegaptanib, thermal laser, or photodynamic therapy with or without triamcinolone acetonide administration, was performed. All patients were refractory to previous treatment. They received monthly injections of bevacizumab and were followed by clinical examination, angiography, and OCT. RESULTS: Nine of 10 patients had stable or improved vision. Angiogram findings showed resolution of leakage from CNVMs. OCT demonstrated resolution of the subretinal or intraretinal fluid but persistence of the PED itself. Vision improvement was correlated with OCT changes. CONCLUSION: Intravitreal bevacizumab may be a viable option in treating patients with fibrovascular PEDs. OCT findings suggest that visual improvement is secondary to resolution of subretinal and intraretinal edema without resolution of the PED.     

Subthreshold transpupillary thermotherapy for subfoveal occult choroidal neovascularization secondary to age-related macular degeneration

PURPOSE: To describe the long term outcome of patients with subfoveal, occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) treated with subthreshold transpupillary thermotherapy. METHODS: 82 eyes of 82 consecutive patients with subfoveal occult CNV secondary to AMD were treated with subthreshold transpupillary thermotherapy. Best corrected visual acuity, fundus photography, fluorescein and indocyanine green angiography were performed. RESULTS: All patients have been followed for at least 24 months. At the final follow-up visit, 75.6% of patients had stable or improved visual acuity and 24.4% had worsened visual acuity. No overtreatment side effects were found. CONCLUSION: Subthreshold transpupillary thermotherapy seems effective in stabilizing visual acuity in patients affected by occult, subfoveal CNV even on a long-term basis.     

Subthreshold transpupillary thermotherapy for subfoveal occult choroidal neovascularization secondary to age-related macular degeneration

Purpose. To describe the long term outcome of patients with subfoveal, occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) treated with subthreshold transpupillary thermotherapy. Methods. 82 eyes of 82 consecutive patients with subfoveal occult CNV secondary to AMD were treated with subthreshold transpupillary thermotherapy. Best corrected visual acuity, fundus photography, fluorescein and indocyanine green angiography were performed. Results. All patients have been followed for at least 24 months. At the final follow-up visit, 75.6% of patients had stable or improved visual acuity and 24.4% had worsened visual acuity. No overtreatment side effects were found. Conclusion. Subthreshold transpupillary thermotherapy seems effective in stabilizing visual acuity in patients affected by occult, subfoveal CNV even on a long-term basis.