Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration

PURPOSE: To describe the development of new and enlargement of preexisting atrophy confined to areas with abnormally high levels of in vivo autofluorescence in eyes with geographic atrophy (GA) associated with age-related macular degeneration (ARMD). METHODS: The spatial distribution and intensity of fundus autofluorescence as well as the spread of GA and occurrence of new GA was recorded over a period of 3 years in three patients with ARMD using a confocal scanning laser ophthalmoscope. RESULTS: A diffuse irregular increased autofluorescence at the posterior pole was recorded at baseline in the presence of unifocal or multifocal patches of geographic atrophy. Within these areas of elevated autofluorescence, new atrophic areas developed, and existing patches of atrophy enlarged during the review period, whereas this was not observed in areas with normal background autofluorescence. The total area of abnormal autofluorescence also showed enlargement over time. CONCLUSIONS: These preliminary findings suggest that areas of increased autofluorescence precede the development and enlargement of outer retinal atrophy in eyes with ARMD. Because the dominant fluorophores of fundus autofluorescence are part of lipofuscin granules of RPE cells, the observations indicate that excessive RPE lipofuscin accumulation may be of significance in the pathogenesis of GA associated with ARMD. With GA being a major cause for severe visual loss in ARMD, in vivo fundus autofluorescence recording over time may allow identification of prognostic determinants and may give important clues to the understanding of mechanisms of disease.     

Phenotypic variation of retinal pigment epithelium in age-related macular degeneration.

PURPOSE: To determine whether retinal pigment epithelium (RPE) in eyes with age-related macular degeneration (ARMD) express vimentin and alpha smooth muscle actin (alphaSMA), two cytoskeletal proteins associated with phenotypic variation in culture. METHODS: Six eyes with late ARMD and three age-matched control eyes were preserved in buffered 4% paraformaldehyde and cryosectioned at 10 microm. Stages of RPE morphology and pigmentation were assessed by the Alabama Age-Related Macular Degeneration Grading System. Vimentin, alphaSMA, and glial fibrillary acidic protein (GFAP) expression was detected by indirect immunofluorescence. These results were compared with regional variations in disease severity. RESULTS: RPE changes in ARMD included acquired expression of vimentin, but alphaSMA-positive cells were rare. GFAP expression increased in Müller cells in the neural retina in association with RPE changes and photoreceptor degeneration. CONCLUSIONS: The initial stages of RPE changes in eyes with ARMD mimic those reported for cultured RPE cells. The absence of alphaSMA-positive cells in regions of RPE atrophy suggests that RPE are lost rather than persist in a dedifferentiated state.     

Distribution of pigment epithelium autofluorescence in retinal disease state recorded in vivo and its change over time

· Background: Recently a technique of imaging the retinal pigment epithelium (RPE) has been developed that takes advantages of its intrinsic fluorescence derived from lipofuscin. The purpose of this study was to document the distribution of fundus autofluorescence in patients with various retinal diseases and its change over time. · Methods: The intensity and spatial distribution of fundus autofluorescence was documented in 318 eyes from 159 patients with various retinal diseases using a confocal Laser Scanning Ophthalmoscope. Thirty patients with macular dystrophies and 30 with age-related macular disease underwent serial examinations over a period of 1–3 years in order to monitor the changes over time of fundus autofluorescence. · Results: Absent autofluorescence corresponded well spatially with outer retinal atrophy in eyes with retinitis pigmentosa and rod-cone dystrophy. Abnormally high background autofluorescence was seen in the macular region in some patients with dominant and recessive retinitis pigmentosa and rod-cone dystrophies. In areas of macular edema fundus autofluorescence was abnormal. Fundus autofluorescence showed changes over time in most of the eyes with retinal diseases studied. · Conclusion: Fundus autofluorescence allows documentation of areas of photoreceptor cell loss in eyes with retinitis pigmentosa and rod-cone dystrophies. If abnormal high background autofluorescence in the surviving areas occurs only in some patients with retinitis pigmentosa, the technique may serve to distinguish the regional from the diffuse type of disease. Over time, fundus autofluorescence may demonstrate change or may remain stable. Received: 14 August 1997 Revised version received: 28 January 1998 Accepted: 4 March 1998     

Correlation between the area of increased autofluorescence surrounding geographic atrophy and disease progression in patients with AMD

PURPOSE: To test the hypothesis that the extension of areas with increased fundus autofluorescence (FAF) outside atrophic patches correlates with the rate of spread of geographic atrophy (GA) over time in eyes with age-related macular degeneration (AMD). METHODS: The database of the multicenter longitudinal natural history Fundus Autofluorescence in AMD (FAM) Study was reviewed for patients with GA recruited through the end of August 2003, with follow-up examinations within at least 1 year. Only eyes with sufficient image quality and with diffuse patterns of increased FAF surrounding atrophy were chosen. In standardized digital FAF images (excitation, 488 nm; emission, >500 nm), total size and spread of GA was measured. The convex hull (CH) of increased FAF as the minimum polygon encompassing the entire area of increased FAF surrounding the central atrophic patches was quantified at baseline. Statistical analysis was performed with the Spearman's rank correlation coefficient (rho). RESULTS: Thirty-nine eyes of 32 patients were included (median age, 75.0 years; interquartile range [IQR], 67.8-78.9); median follow-up, 1.87 years; IQR, 1.43-3.37). At baseline, the median total size of atrophy was 7.04 mm2 (IQR, 4.20-9.88). The median size of the CH was 21.47 mm2 (IQR, 15.19-28.26). The median rate of GA progression was 1.72 mm2 per year (IQR, 1.10-2.83). The area of increased FAF around the atrophy (difference between the CH and the total GA size at baseline) showed a positive correlation with GA enlargement over time (rho=0.60; P=0.0002). CONCLUSIONS: FAF characteristics that are not identified by fundus photography or fluorescein angiography may serve as a prognostic determinant in advanced atrophic AMD. As the FAF signal originates from lipofuscin (LF) in postmitotic RPE cells and since increased FAF indicates excessive LF accumulation, these findings would underscore the pathophysiological role of RPE-LF in AMD pathogenesis.     

Progression of geographic atrophy and impact of fundus autofluorescence patterns in age-related macular degeneration

PURPOSE: To test if fundus autofluorescence (FAF) patterns around geographic atrophy (GA) have an impact on GA progression rates over time in atrophic age-related macular degeneration (AMD). DESIGN: Prospective longitudinal multicenter natural history study. METHODS: Standardized digital FAF images were obtained from 195 eyes of 129 patients with GA using confocal scanning laser ophthalmoscopy (excitation 488 nm, emission >500 nm). Areas of GA were quantified and patterns of abnormal FAF in the junctional zone were classified. Repeated FAF images were obtained over a median follow-up period of 1.80 years (interquartile range [IQR], 1.28 to 3.34). RESULTS: Areas of GA (median, 7.04 mm(2) at baseline; IQR, 3.12 to 10.0) showed a median enlargement of 1.52 mm(2)/year (IQR, 0.81 to 2.33). Progression rates in eyes with the banded (median 1.81 mm(2)/year) and the diffuse FAF pattern (1.77 mm(2)/year) were significantly higher compared to eyes without FAF abnormalities (0.38 mm(2)/year) and focal FAF patterns (0.81 mm(2)/year, P < .0001). Within the group of the diffuse pattern, eyes with a diffuse trickling pattern could be identified that exhibited an even higher spread rate (median 3.02 mm(2)/year) compared to the other diffuse types (1.67 mm(2)/year, P = .001). CONCLUSIONS: The results indicate that distinct phenotypic FAF patterns have an impact on disease progression in eyes with atrophic AMD and may therefore serve as prognostic determinants. The findings underscore the relevance of FAF imaging and the pathogenetic role of excessive retinal pigment epithelium (RPE) lipofuscin (LF) accumulation in GA. Natural history data and identification of high-risk characteristics will be helpful to design interventional studies aiming at slowing the spread of atrophy.     

Multimodal imaging of dry age‐related macular degeneration

Purpose: The purpose of this study was to understand clinical significance of near‐infrared reflectance (NIR), blue fundus autofluorescence (FAF) and near‐infrared autofluorescence (NIA) in dry age‐related macular degeneration (AMD), by correlation with fluorescein angiography (FA) and cross‐sectional spectral domain optical coherence tomography (SD OCT). Methods: We evaluated 110 eyes (62 patients, mean age: 64 ± 8 years) diagnosed with dry AMD between January 2010 and December 2010, which underwent NIR (λ = 830 nm), FAF and FA (excitation λ = 488 nm; emission λ > 500 nm), NIA (excitation λ = 787 nm; emission λ > 800 nm), and simultaneous SD OCT scanning using a combined confocal scanning laser ophthalmoscope/SD OCT device (Spectralis HRA + OCT; Heidelberg Engineering, Heidelberg, Germany). Results: Drusen showed variable increased/decreased NIR, FAF, NIA and FA, which corresponded to variable increased/decreased thickness of the retinal pigment epithelium (RPE) and possible presence of subretinal deposits on SD OCT. Geographic atrophy (GA) was present in 43/110 eyes (39.0%) and showed increased NIR and fluorescence (FA), absent FAF and NIA, and loss of RPE on SD OCT. The hyperautofluorescence of the GA margin was never larger in FAF than that in NIA, while in 16.2% of cases, it was larger in NIA than that in FAF and corresponded to mild choroidal hyperreflectivity on SD OCT. Conclusions: Simultaneous recording of SD OCT scans provided ultrastructural data for the evaluation of NIR, FAF, NIA and FA in dry AMD. Near‐infrared autofluorescence might detect earlier than FAF areas of RPE cell loss at the GA margin.     

Topographic, 3D and Quantitative analysis of autofluorescence in dry, age-related macular degeneration

OBJECTIVE: Autofluorescence of the retina allows one to quantify and follow the extent and progression of dry, age-related macular degeneration (ARMD) changes. The objective of this study was to compare different analysis methods for displaying autofluorescence images. METHODS: In a consecutive series of 15 patients with mild dry AMD and 15 patients without retinal pathologies, one 30 degrees autofluorescence image was obtained with the Heidelberg retina angiograph (HRA). Evaluation was performed by observers masked to the clinical group for each of the three analysis displays: topographic map in false colours (similar to height lines in maps), 3D display of optical density and quantitative, standardised evaluation of optical density values. RESULTS: For the 30 eyes included, grading of ARMD versus normal yielded a sensitivity of 83 -92 % for the topographic map, 58 - 83 % for the 3D and 75 - 83 % for quantitative optical density display. The corresponding specificity was 87 - 93 % for the topographic map, 53 - 60 % for the 3D and 67 - 80 % for the quantitative optical density display. CONCLUSIONS: Analysis by topographic mapping is suitable to supply quantitative information of optical density for evaluating autofluorescence images. In spite of being illustrative, a 3D display of optical density does not offer sufficient properties for analysis.     

Retinal angiomatous proliferation in age-related macular degeneration

BACKGROUND: Angiomatous proliferation in ARMD originates from the retina and extends into the subretinal space. Retinal angiomatous proliferation (RAP) is diagnosed with angiography. This study investigates the characteristics of RAP in optical coherence tomography (OCT) and correlates them with clinical and fluorescein angiographic findings. METHODS: 327 consecutive patients with age-related macular degeneration (ARMD) were retrospectively examined using a standardised protocol. The protocol included best corrected visual acuity (BCVA), binocular ophthalmoscopy, fundus photography, fluorescein angiography (FAG) and OCT. The OCT and angiographic findings were graded in 3 RAP stages. RESULTS: 32 of 327 (9.79 %) patients (45 eyes) had RAP. The age ranged from 56 to 90 years (median: 79 years). 9 eyes presented RAP stage I, 23 stage II and 13 stage III. BCVA ranged from 0.01 to 0.7 (median: 0.2). OCT foveal minimum was 136 to 722 microns (median: 327). 33 (73 %) eyes showed a detachment of retinal pigment epithelium (RPE). Macular oedema was found in 43 (96 %) eyes. Cystoid macular oedema was seen in 36 (80 %) eyes. In stage II, 22 eyes (96 %) showed an RPE detachment, in stage III 11 eyes (85 %). 11 (85 %) eyes in stage III showed retinal-choroidal anastomosis. CONCLUSIONS: RAP was found in 9.79 % of the patients with ARMD. The OCT is helpful in detection of RPE detachment, macular oedema and cystoid changes in RAP. RAP and retinal-choroidal anastomosis should be identified because of the possibly poor prognosis.     

Fundus autofluorescence imaging findings in retinal pigment epithelial tear

PURPOSE: Retinal pigment epithelial (RPE) tear is a clinical and angiographic entity, which usually occurs in association with pigment epithelial detachments (PED), in the context of neovascular age-related macular degeneration (ARMD). The recording of fundus autofluorescence (FAF) has been introduced as a technique of retinal imaging, allowing the in vivo assessment of the integrity of RPE. The authors describe the FAF imaging findings in a patient with RPE tear. METHODS: Observational case report. RESULTS: A 70-year-old woman developed RPE tear after the application of photodynamic therapy for choroidal neovascularization associated with PED. The diagnosis of the RPE tear was confirmed by fluorescein angiography (FA) and indocyanine green angiography (ICGA). FAF imaging revealed absence of autofluorescence at the area which was denuded of RPE, while at the area where the RPE was rolled, a heterogeneous signal of FAF was recorded. The intensity of the signal in that area was, on average, not different from the normal background FAF signal expected in an unaffected RPE/photoreceptor complex. CONCLUSIONS: The authors report the FAF imaging findings in a patient with RPE tear. These findings can be interpreted from the ability of FAF imaging to access in vivo the integrity of RPE, and correlate well with the histopathology of this clinical entity. FAF imaging, as a fast and noninvasive technique, may be a useful modality, alternative to FA and ICGA, in the diagnosis and evaluation of such cases. Moreover, it may contribute to a more detailed phenotyping of the various clinical pictures associated with neovascular ARMD.     

Treatment of massive subretinal hematoma associated with age-related macular degeneration using vitrectomy with intentional giant tear

The purpose of this study was to report the surgical outcomes after creating a 120° intentional giant retinal tear for use in removing hemorrhage and subretinal proliferative tissue in patients with polypoidal choroidal vasculopathy (PCV) or age-related macular degeneration (ARMD). This study involved 12 eyes of 12 patients (10 eyes: PCV, 2 eyes: ARMD). After removal of the lens in phakic eyes, we performed a vitrectomy with artificial posterior vitreous detachment. Subsequently, a 120° intentional giant retinal tear was created in the temporal periphery, the retina was then turned, and the subretinal hemorrhage and proliferative tissue were removed. In order to preserve as much of the retinal pigment epithelium (RPE) as possible, we used a bimanual technique under direct visualization. After stretching the retina by use of perfluorocarbon liquid (PFCL), we performed endophotocoagulation around the tear followed by PFCL/silicone oil exchange. Except for 1 eye in which extensive loss of the RPE occurred, the fundus findings and the visual acuity (VA) improved in all patients. In addition, postoperative VA improved to ≥20/50 in 3 eyes in which the macular RPE was preserved. This surgical procedure is an effective treatment for PCV or ARMD patients with extensive subretinal hemorrhage and proliferative tissue.     

Surgical management of subfoveal choroidal neovascularization.

BACKGROUND: Subfoveal choroidal neovascularization (CNV) usually is associated with a poor visual prognosis. Laser photocoagulation of certain subfoveal membranes secondary to age-related macular degeneration (ARMD) appears preferable to observation based on recent Macular Photocoagulation Study (MPS) findings but is associated with decreased vision. The authors explored the use of vitreoretinal surgical techniques as an alternative method of eradicating subfoveal CNV. METHODS: After vitrectomy, a small retinotomy technique was used to extract or disconnect from the choroidal circulation subfoveal CNV in 58 eyes. There were 33 eyes with ARMD, 20 eyes with presumed ocular histoplasmosis, and 5 eyes with miscellaneous etiologies. Five eyes also received subfoveal RPE patches. RESULTS: With limited follow-up, significant improvement in vision (defined as 2 Snellen lines) was achieved in 7 of 22 eyes with ARMD CNV removal (1 eye 20/20), 0 of 4 eyes with ARMD CNV removal and RPE patches, and 1 of 7 eyes with ARMD CNV disconnection. Significant improvement was achieved in 6 of 16 eyes with presumed ocular histoplasmosis removal and 0 of 4 eyes with presumed ocular histoplasmosis CNV disconnection. In 5 eyes with miscellaneous CNV, 2 improved (20/20 and 20/40). CNV recurred in 29%. CONCLUSIONS: Some patients with subfoveal CNV appear to benefit from surgical removal. Only rarely do eyes with ARMD improve. Longer-term follow-up and refined case selection are required before this approach can be widely recommended.     

Classification of abnormal fundus autofluorescence patterns in the junctional zone of geographic atrophy in patients with age related macular degeneration

AIM: To describe and classify patterns of abnormal fundus autofluorescence (FAF) in the junctional zone of geographic atrophy (GA) in patients with age related macular degeneration. METHODS: Digital FAF images were recorded in 164 eyes of 107 patients using a confocal scanning laser ophthalmoscope (cSLO; excitation 488 nm, detection above 500 nm) as part of a prospective multicentre natural history study (FAM Study). FAF images were obtained in accordance with a standardised protocol for digital image acquisition and generation of mean images after automated alignment. RESULTS: Image quality was sufficient for classification of FAF patterns in 149 eyes (90.9%) with lens opacities being the most common reason for insufficient image quality. Abnormal FAF outside GA in 149 eyes was classified into four patterns: focal (12.1%), banded (12.8%), patchy (2.0%), and diffuse (57.0%), whereby 12.1% had normal background FAF in the junctional zone. In 4% there was no predominant pattern. The diffuse pattern was subdivided into four groups including reticular (4.7%), branching (27.5%), fine granular (18.1%), and fine granular with peripheral punctate spots (6.7%). CONCLUSIONS: Different phenotypic patterns of abnormal FAF in the junctional zone of GA can be identified with cSLO FAF imaging. These distinct patterns may reflect heterogeneity at a cellular and molecular level in contrast with a non-specific ageing process. A refined phenotypic classification may be helpful to identify prognostic determinants for the spread of atrophy and visual loss, for identification of genetic risk factors as well as for the design of future interventional trials.     

视网膜色素上皮、Bruch膜及脉络膜的老年性黄斑变性改变

目的研究并定量分析视网膜色素上皮(retinalpigment epithelium,RPE)、Bruch膜和脉络膜的老年性改变及在老年黄斑变性眼的改变。方法应用改良Masson三色组织染色法及电脑图像分析软件,对36例不同龄正常眼及6例老年黄斑变性(age—related macular degenera—tion,ARMD)眼的RPE数量和形态、Bruch膜的厚度和脉络膜毛细血管的密度及脉络膜厚度进行定量分析研究及讨论。结果RPE老年性形态改变包括数量的减少及细胞高度的增加伴有Bruch膜增厚(老年性黄斑变性);但脉络膜毛细血管密度及脉络膜的厚度与年龄未见明显的关系。ARMD眼主要表现为RPE形态明显改变及基底膜线样沉着物形成,Bruch膜增厚。结论RPE以及Bruch膜的改变可能是早期和基础性的老年性改变,其进一步的变化可能导致脉络膜及视网膜的损害。     

Fundus autofluorescence and fundus perimetry in the junctional zone of geographic atrophy in patients with age-related macular degeneration

PURPOSE: To investigate retinal sensitivity in the junctional zone of geographic atrophy (GA), with variations in fundus autofluorescence (FAF) in patients with advanced age-related macular degeneration (AMD). METHODS: The spatial distribution and intensity of FAF were recorded with a confocal scanning laser ophthalmoscope (SLO). Eyes had normal background FAF (group 1) or increased FAF (group 2) surrounding the atrophic patches. Retinal sensitivity was assessed by applying light stimuli with static automated full-threshold fundus perimetry with a modified SLO. Threshold sensitivities were compared with age-matched normal sensitivities. RESULTS: Thirty-nine eyes of 39 patients with GA were included. Group 2 had a higher percentage of all test points outside the GA area, with decreased retinal sensitivity (44.9% +/- 28.7%) compared with group 1 (20.7% +/- 12.7%; P = 0.0063; multiple regression model; outcome variable is retinal sensitivity; covariates are group affiliation and GA area). Within group 2, the average percentage of stimuli in areas of normal FAF with reduced sensitivity was 38.0% +/- 33.0%, whereas the average percentage of stimuli in areas of elevated FAF with reduced sensitivity was 52.6% +/- 29.7% (P = 0.023, Wilcoxon signed rank test). CONCLUSIONS: Areas of increased FAF outside GA may be associated with variable degrees of loss of retinal sensitivity and suggest a functional correlate of excessive accumulation of retinal pigment epithelium lipofuscin in AMD. Combining in vivo recording of FAF and retinal sensitivity, using SLO technology, may give important clues in the understanding of mechanisms of disease.     

眼底自发荧光在年龄相关性黄斑变性中的应用指南(2023)

眼底自发荧光(FAF)成像是基于视网膜色素上皮和脉络膜中的眼内源性荧光团激发的荧光进行成像的技术,荧光激发物质主要是脂褐质(LF)和黑色素。由于该无创检查技术可通过观察LF和黑色素在眼底的空间分布来反映视网膜色素上皮的功能状况,在诊断、鉴别和随访年龄相关性黄斑变性(ARMD)上具有独特优势。本指南即对FAF在ARMD不同阶段和分类上的临床应用进行规范和解读。     

Two-photon-excited fluorescence imaging of human RPE cells with a femtosecond Ti:Sapphire laser

PURPOSE: To record the distribution and spectrum of human retinal pigment epithelial cell lipofuscin (LF) by two-photon-excited fluorescence (TPEF) and confocal laser scanning microscopy. METHODS: Ex vivo TPEF imaging of the human retinal pigment epithelium (RPE) of human donor eyes was conducted with a multiphoton laser scanning microscope that employs a femtosecond Ti:sapphire laser as an excitation laser source. The spectrum of autofluorescence of LF granules was analyzed with a confocal laser scanning microscope coupled to a UV argon laser. RESULTS: TPEF examination allowed for imaging of RPE cell morphology and intracellular distribution of LF granules with high-contrast and submicrometer resolution. Variations in cell size and shape as well as in autofluorescence spectra of individual LF granules were recorded. The typical diameter of LF granules was found to be below 1 mum, with some RPE cells possessing larger granules. Remarkably, enhanced blue-green autofluorescence was observed from these larger LF granules. CONCLUSIONS: TPEF imaging represents a novel tool for the investigation of morphologic and spectral characteristics of human RPE cells. Spectral variations of individual LF granules may indicate differences in the complex molecular composition. Compared to conventional single-photon excited autofluorescence, TPEF with a tunable laser source allows for reduced photo damage and deeper sensing depth. It may help to elucidate further the pathophysiological role of LF accumulation as a common downstream pathogenetic pathway in retinal diseases. With the proof of principle from this ex vivo study, further work is now planned to evaluate the safety of TPEF RPE imaging in RPE cultures and animal models.     

Ultrastructural localization of lipid peroxides as benzidine-reactive substances in the albino mouse eye

· Background: Lipid peroxidation is considered to be a prominent feature of retinal degeneration and has also been proposed to be involved in the pathogenesis of age-related macular degeneration. Melanin protects against lipid peroxidation and takes part in the detoxification of lipid peroxides (LP). LP can be ultrastructurally detected as benzidine-reactive substances (BRS) using tetramethylbenzidine (TMB). Albino mice lack melanin. In the present study, LP were localized as BRS in the eyes of albino and pigmented mice. · Methods: Eye cups of an albino mouse lineage and of wild-type mice were fixed with 2% glutaraldehyde, incubated with 0.5 mg/ml TMB and embedded for electron microscopy. · Results: BRS were detected in the eyes of albino mice, but no reaction product was seen in pigmented eyes. BRS located in the retinal pigment epithelium (RPE) and in the choroid of the albino mouse; no BRS were found in intact rod outer segments (ROS). · Conclusion: The lack of melanin in albino mice is associated with a higher level of lipid peroxidation in RPE and choroid. Melanin seems to protect against LP in RPE and choroid. A lack of melanin is not associated with lipid peroxidation in intact ROS. The present investigation demonstrates the significance of melanin in protection against LP in RPE and choroid. Received: 16 November 1998 Revised version received: 18 January 1999 Accepted: 19 January 1999     

Predictors of drusen reduction after subthreshold infrared (810 nm) diode laser macular grid photocoagulation for nonexudative age-related macular degeneration

PURPOSE: To determine the predictors of drusen reduction in eyes with nonexudative age-related macular degeneration (ARMD) treated with subthreshold infrared (810 nm) diode laser macular grid photocoagulation. Additionally, to determine the relationship of laser-induced drusen reduction and best-corrected visual acuity (BCVA) 18 months after laser treatment.DESIGN: Randomized controlled clinical trial.METHODS: Fifty patients (100 eyes) with bilateral nonexudative ARMD were enrolled at two centers. One eye of each patient was randomized to the observation; the other eye was treated with 48 subthreshold (invisible end point) applications of infrared (810 nm) diode laser in a macular grid pattern. The eyes that received subthreshold laser treatment were compared with the eyes that received no treatment. The baseline fundus characteristics (number, size, and distribution of drusen, as well as focal hyperpigmentation) from two macula areas (central 1500 micro diameter, pericentral 1500 micro ring area) on stereo color photographs, the number of laser-induced lesions, and the area of laser induced retinal pigment epithelial (RPE) lesions on fluorescein angiography 3 months after treatment were studied as predictors of major drusen reduction (> or = 50% drusen reduction from baseline) 18 months after laser treatment. BCVA at baseline and 18 months later was compared in observation eyes and in laser-treated eyes.RESULTS: Eighteen months after randomization, 24 (48%) of 50 eyes treated with subthreshold laser had major drusen reduction compared with three (6%) of 50 observation eyes (P =.00001). At 3 months post-treatment in laser-treated eyes with major drusen reduction, the mean number of laser-induced lesions on fluorescein angiography was 30.7 and the mean area of RPE change was 0.81 mm(2) compared with 14.8 laser-induced lesions and 0.35 mm(2) area of RPE change in eyes without major drusen reduction (P =.0001 and P =.0003, respectively). At baseline, fundus characteristics were not significantly different between observation eyes and laser-treated eyes or between the major drusen reduction group and the nonmajor drusen reduction group. At 18 months after treatment, BCVA was not significantly different in laser-treated eyes and in observation eyes.CONCLUSIONS: Subthreshold infrared (810 nm) diode laser macular grid photocoagulation in eyes with nonexudative ARMD significantly reduced drusen 18 months after laser treatment. Both the number of subthreshold laser lesions and the area of RPE changes visible on fluorescein angiography 3 months after treatment appeared to be predictors for major drusen reduction 18 months after treatment. However, it remains to be determined whether laser-induced drusen reduction is beneficial for visual acuity or reduces the incidence of choroidal neovascularization (CNV) in eyes with nonexudative ARMD.     

Fundus autofluorescence after full macular translocation surgery for myopic choroidal neovascularization

BACKGROUND: To investigate fundus autofluorescence (FAF) findings in patients who underwent full macular translocation surgery with 360-degree retinotomy (MT360) for myopic choroidal neovascularization (CNV). METHODS: Observational case series. Thirty-one eyes of 31 patients who underwent MT360 for myopic CNV from February 1999 through September 2005 were included. We measured the best-corrected visual acuity and obtained color fundus photographs, optical coherence tomography (OCT) images, and fluorescein angiography images. FAF imaging by confocal scanning laser ophthalmoscope was obtained postoperatively in all study eyes and preoperatively in two study participants. FAF features at the new macula were qualitatively evaluated and compared with preoperative lesions associated with CNV. The FAF features at the retinal pigment epithelial (RPE) area with preoperative CNV also were evaluated. RESULTS: The mean interval between MT360 and the final FAF examination was 58 months (range, 8-94 months). FAF imaging was almost normal in five eyes (16%), the increased FAF was well defined at the new macula area in 23 eyes (74%), and the FAF was decreased in three eyes (10%). Neither newly developed CNV nor subretinal fluid was seen at the new macular region in any eyes on fluorescein angiography or OCT imaging. The configurations of well-defined increased FAF in 23 eyes corresponded with the preoperative CNV in two eyes (9%) and subretinal hemorrhages in five eyes (22%). Well-defined increased FAF larger than the CNV or subretinal hemorrhage was seen in 16 eyes (69%). The RPE area located at the area of the preoperative CNV had a FAF defect or decreased FAF in 30 eyes (97%) on postoperative FAF imaging; there were no increased FAF changes. CONCLUSIONS: Well-defined increased FAF at the new macula after MT360 suggests that FAF reflects not only fluorophores in the RPE but also in the neurosensory retina. These fluorophores may result from interactions between the retina and CNV/pathologic RPE.     

Allogenic fetal retinal pigment epithelial cell transplant in a patient with geographic atrophy

PURPOSE: To test the hypothesis that healthy fetal retinal pigment epithelium (RPE) can rescue the remaining viable RPE and choriocapillaries and thereby the photoreceptors in non-neovascular age-related macular degeneration (ARMD) (geographic atrophy [GA]). METHODS: A 65-year-old legally blind woman with non-neovascular ARMD underwent fetal RPE transplantation. Best-corrected visual acuity testing, detailed fundus examination, fundus photography, fluorescein angiography, scanning laser ophthalmoscope macular perimetry, and humoral and cellular immune response testing were performed. A suspension of RPE was infused into the subretinal space through a retinotomy along the superotemporal arcade at the edge of the area of GA. The patient did not take systemic immunosuppressants. RESULTS: The patient's vision remained unchanged for 5 months after the surgery. Fluorescein angiography after transplantation showed leakage and staining at the level of the outer retina. There was progressive subretinal fibrosis in the area of the transplant. Immune response studies showed a weakly positive mixed lymphocyte response against phosducin and rhodopsin. CONCLUSION: Although it is surgically feasible to transplant fetal RPE to the subretinal space of patients with GA, such an allogenic RPE transplant without immunosuppression leads to leakage on fluorescein angiography and eventual fibrosis. A very weak immune response against proteins associated with photoreceptors is also of concern.