Increased Fundus Autofluorescence Research Articles

Primary versus Secondary Elevations in Fundus Autofluorescence.

The method of quantitative fundus autofluorescence (qAF) can be used to assess the levels of bisretinoids in retinal pigment epithelium (RPE) cells so as to aid the interpretation and management of a variety of retinal conditions. In this review, we focused on seven retinal diseases to highlight the possible pathways to increased fundus autofluorescence. ABCA4- and RDH12-associated diseases benefit from known mechanisms whereby gene malfunctioning leads to elevated bisretinoid levels in RPE cells. On the other hand, peripherin2/RDS-associated disease (PRPH2/RDS), retinitis pigmentosa (RP), central serous chorioretinopathy (CSC), acute zonal occult outer retinopathy (AZOOR), and ceramide kinase like (CERKL)-associated retinal degeneration all express abnormally high fundus autofluorescence levels without a demonstrated pathophysiological pathway for bisretinoid elevation. We suggest that, while a known link from gene mutation to increased production of bisretinoids (as in ABCA4- and RDH12-associated diseases) causes primary elevation in fundus autofluorescence, a secondary autofluorescence elevation also exists, where an impairment and degeneration of photoreceptor cells by various causes leads to an increase in bisretinoid levels in RPE cells.

North Carolina macular dystrophy shows a particular drusen phenotype and atrophy progression

Background/AimTo provide a comprehensive multimodal retinal imaging characterisation of patients with North Carolina macular dystrophy (NCMD).MethodsClinical evaluation and retinal imaging in six families.ResultsTwenty-one subjects showed phenotypic characteristics of NCMD ....

Quantitative fundus autofluorescence in smokers compared to non-smokers

Increased fundus autofluorescence is directly related to increased RPE lipofuscin deposition in the retina and has been observed in eyes with age-related macular degeneration (AMD). Smoking is the most significant modifiable risk factor for the development and progression of AMD, in which one of the main mechanisms is oxidative damage from smoking leading to RPE cell toxicity. The relationship between smoking and autofluorescence is not established and could provide insight into pathogenic mechanism of AMD. Therefore, our objective was to compare quantitative fundus autofluorescence (qAF) in the retinae of healthy non-smokers to smokers. We conducted a cross-sectional study at the 2016 Minnesota State Fair. Participants self-reported past medical and ocular history and underwent eye examination as well as qAF imaging with Spectralis confocal scanning laser ophthalmoscope (cSLO) equipped with an internal fluorescent reference. Two sets of images were obtained per eye. Stepwise multiple mixed effects regression model was used to examine the relationship between mean qAF values and smoking status. We enrolled 105 individuals (54 smokers, 61 females, mean age 41 years with range 18–78 years old). Fundus autofluorescence images were analyzable for 85 of 105 individuals contributing 161 eyes (80 right, 81 left). The repeatability coefficients between the first set and second set of images were ±21% of their mean qAF values. Older age and female gender were independently associated with higher qAF. Positive smoking history tended to result in higher qAF values after adjusting for age and gender but was not statistically significant (0.118, 95%CI -0.003, 0.240, P = 0.056). Among smokers, the number of pack-years smoked was not significantly associated with higher qAF. Our study's results are consistent with existing literature in which older age is predictive of intensified autofluorescence, while smoking history does not have as important of an impact on autofluorescence as hypothesized. Several large epidemiological studies have shown that smoking is significantly associated with AMD, and qAF is likely not the appropriate modality to clinically assess smoking's impact on retinae.

PIGMENTED PARAVENOUS CHORIORETINAL ATROPHY: Detailed Clinical Study of a Large Cohort.

To review and describe in detail the demographics, functional and anatomical characteristics, and clinical course of pigmented paravenous chorioretinal atrophy in a large cohort of adults and children. This is a retrospective case series of consecutive patients diagnosed with pigmented paravenous chorioretinal atrophy at a single U.K. referral center from 1974 to 2016. Clinical records, retinal imaging (color fundus photography, fundus autofluorescence, and optical coherence tomography), and electrophysiological assessments were reviewed. Twenty-three patients were identified (13 males and 10 females). The mean age at presentation was 35 years (range 10-67 years). Mean follow-up was 6.7 years (range 0-30 years). There was no family history of similar retinal disease. Thirteen (57%) patients were asymptomatic. Symptoms included photopsia (n = 1.4%), blurred vision (n = 4.17%), peripheral visual field loss (n = 3.13%), and nyctalopia (n = 2.8%). One patient had previous intermediate uveitis. Twenty-one (91%) patients had ≥6/12 in the better seeing eye at final follow-up; visual acuity loss over time was recorded in 2 patients. Color vision was normal in all 14 patients assessed. Paravenous hypoautofluorescence with surrounding increased fundus autofluorescence was characteristically observed. Optical coherence tomography over the retinal changes demonstrated choroidal, retinal pigment epithelium, and outer retinal layer thinning. Peripapillary atrophic changes on fundus photography were evident in 20 (87%) patients. Interocular asymmetry of fundus and electroretinography findings was common. The electroretinography findings showed a similar degree of generalized rod and cone photoreceptor dysfunction in most cases. Overall, most patients with pigmented paravenous chorioretinal atrophy maintained stable vision. The lack of other affected family members, slow or absent progression, and interocular asymmetry of the retinal features is suggestive of an acquired rather than inherited retinal disorder, which is generally nonprogressive. We identify that patients commonly have marked interocular asymmetry both on structural and functional assessment.

The Phenotypic Spectrum of Ophthalmic Changes in CEP290 Mutations

Inherited retinal diseases (IRDs) may be caused by variations in genes affecting the connecting cilium of photoreceptor cells and intraflagellar transport, manifested as ciliopathies. CEP290 is frequently mutated in non-syndromic, but also syndromic IRDs. In preparation for clinical treatment trials, detailed phenotypic work-up including longitudinal follow-up is mandatory. We performed genotype-phenotype correlations in 30 patients with biallelic mutations in CEP290. The study was approved by the IRB of the medical faculty of the Justus-Liebig University Giessen. The patients received a comprehensive clinical examination, including spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) recording, and electrophysiology whenever possible. Thirty patients aged 1 month to 84 years (median at first visit 0.6 y) were followed between 5 months and 25.7 years (median 4.8 y). Twenty-three of these patients carried the c.2991+1655A>G mutation (30/60 allele 2, 7 homozygous). The second most frequent mutation was p.K1575* (9/60 alleles). The full-field electroretinogram showed residual response in a few patients only. After progression, electrophysiological responses were below threshold in all patients. Severely reduced visual acuity persisted from birth. Eight patients had quantifiable best corrected visual acuity (BCVA, logMAR 2 - 0.3), in one case up to the age of 84 y. Absent fixation of targets was noted in 15 patients during the first months of life. Ten of these patients did not improve during follow-up past the second year of life. The other patients developed at least light perception (LP, n = 7) or hand movement (HM, n = 3). Better BCVA was not restricted to the c.2991+1655A>G mutation. Fundus photography documented degenerative changes throughout the retina with macular degeneration and circular increased fundus autofluorescence signals (9/30 patients) in the perimacular ring and in the rod ring, and spotty changes in the periphery. SD-OCT (6/30 patients) disclosed reduced photoreceptor layer (OPL to OS) thickness and preserved inner retinal thickness (RNFL to INL). Better BCVA did not correlate to genotype or central photoreceptor layer thickness. As reported earlier, CEP290 variations are one of the most frequent causes of IRDs with infancy onset. In our patient cohort of 30 patients, only 33% had no LP, 67% at least LP, and among these 26% logMAR 2 to 0.3. Together with preserved ganglion cell and nerve fibre cell layers, success with gene therapeutic approaches appears possible.

Geographic atrophy phenotype identification by cluster analysis

Background/aimsTo identify ocular phenotypes in patients with geographic atrophy secondary to age-related macular degeneration (GA) using a data-driven cluster analysis.MethodsThis was a retrospective analysis of data from a prospective, natural...

Structural Changes in Optical Coherence Tomography Underlying Spots of Increased Autofluorescence in the Perilesional Zone of Geographic Atrophy.

To investigate structural correlates corresponding to the appearance of increased fundus autofluorescence (FAF) in the perilesional area of geographic atrophy (GA) secondary to age-related macular degeneration. Serial FAF images of 181 eyes with GA of 134 patients participating in the Directional Spread in Geographic Atrophy study (NCT02051998) were screened for increased FAF spots that had developed during the review period. Thickness and reflectivity of the retinal pigment epithelium (RPE)-basal lamina complex, as well as the integrity of the external limiting membrane (ELM) and the ellipsoid zone (EZ), respectively, in corresponding optical coherence tomography (OCT) scans were compared between the time points before and after the appearance of increased FAF. Adjacent areas without development of abnormal FAF were assessed as internal control. A total of 36 areas (15 eyes) with de novo developed increased FAF spots and 54 control areas were included. Analysis of the corresponding OCT images revealed an increase in RPE-basal lamina complex thickness (31.8 ± 7.3 to 42.1 ± 11.9 μm [P < 0.001]) and reflectivity (reflectivity ratio: 1.42 ± 0.11 to 1.54 ± 0.27 [P = 0.009]) corresponding to an increased FAF signal while there was no significant change in control areas. Development of increased FAF spots was associated with disruption of the ELM and the EZ. Increase of RPE-basal lamina complex thickness and reflectivity was spatially and temporally associated with the development of increased FAF spots in eyes with GA. In addition, outer retinal disruption may contribute to the corresponding increased FAF signal.

Multimodal Fundus Imaging of Sodium Iodate-Treated Mice Informs RPE Susceptibility and Origins of Increased Fundus Autofluorescence.

PurposeBy multimodal imaging, and the use of mouse and in vitro models, we have addressed changes in fundus autofluorescence (488 and 790 nm) and observed interactions between the photooxidative stress imposed by RPE bisretinoid lipofuscin and the oxidative impact of systemic sodium iodate (NaIO3).MethodsAbca4−/−, wild-type, and Rpe65rd12 mice were given systemic injections of NaIO3 (30 mg/kg). Analysis included noninvasive imaging of fundus autofluorescence (short-wavelength [SW-AF]; near-infrared excitation [NIR-AF]), quantitative fundus AF (qAF; 488 nm); light microscopy, RPE flat-mounts and measurements of outer nuclear layer (ONL) thickness. NaIO3 also was studied by using in vitro assays.ResultsIn SW-AF and NIR-AF images, fundus mottling was visible 3 and 7 days after NaIO3 injection with changes being more pronounced in Abca4−/− mice that are characterized by an abundance of RPE bisretinoid lipofuscin. In Abca4−/− mice, qAF was elevated 3 and 7 days after NaIO3 administration. In light micrographs and RPE flat-mounts stained to reveal tight junctions (ZO-1) and nuclei, the RPE monolayer was disorganized, and clumping and loss of RPE was visible. ONL thinning was most pronounced in Abca4−/− mice. Treatment of ARPE-19 cells with NaIO3 together with the photooxidation of the bisretinoid A2E by exposure to 430-nm light produced an additive effect whereby loss of cell viability was greater than with either perturbation alone.ConclusionsElevations in SW-AF intensity can occur due to photoreceptor cell dysfunction as induced secondarily by NaIO3. Photooxidative stress associated with RPE cell bisretinoid lipofuscin may confer increased susceptibility to the oxidant NaIO3.

Clinical Characterization of CNGB1-Related Autosomal Recessive Retinitis Pigmentosa

There are limited published data on the phenotype of retinitis pigmentosa (RP) related to CNGB1 variants. These data are needed both for prognostic counseling of patients and for understanding potential treatment windows. To describe the detailed clinical and molecular genetic findings in a series of patients with RP with likely pathogenic variants in CNGB1. In this case series, 10 patients from 9 families underwent full ophthalmologic examination. Molecular investigations included whole-exome analysis in 6 patients. The study was conducted from April 17, 2013, to March 3, 2016, with final follow-up completed on March 2, 2016, and data were analyzed from October 27, 2014, to March 29, 2016. Results of ophthalmologic examination and molecular genetic analysis of CNGB1. In this case series, 7 women and 3 men from 9 families with a mean (SD) age of 47.4 (13.2) years identified as having CNGB1 variants were included in this study; there was a mean (SD) follow-up length of 3.7 (2.8) years. The first clinical presentation was with nyctalopia in childhood with visual field loss documented later at a mean (SD) age of 33.2 (8.0) years. All patients had preserved best-corrected visual acuity into adulthood, with a mean of 0.1 logMAR (Snellen equivalent, 20/25) in each eye (logMAR range, 0.0 to 0.3 [Snellen 20/20 to 20/40] in the right eye and -0.1 to 0.3 [Snellen 20/16 to 20/40] in the left eye). Fundus examination revealed midperipheral retinal pigment epithelial atrophy and intraretinal pigment migration. Optical coherence tomography of the macula demonstrated complete preservation of the inner segment ellipsoid band in 1 patient, with variable lateral extent in the other patients corresponding to the diameter of a paracentral ring of increased fundus autofluorescence. Electrophysiologic testing in 6 patients confirmed a rod-cone dystrophy phenotype. Molecular investigations identified a previously reported missense variant (p.[N986I]) and 7 variants not previously reported in disease including 4 nonsense (p.[(Q88*], p.[Q222*], p.[Q318*], and p.[R729*]), 2 frameshift (p.[A1048fs*13], p.[L849Afs*3]), and a splice site variant (c.761 + 2T>A). The data from this study suggest that visual acuity and foveal structure in patients with RP are preserved into adult life such that a lengthy window of opportunity should exist for intervention with novel therapies.

Increased Fundus Autofluorescence and Progression of Geographic Atrophy Secondary to Age-Related Macular Degeneration: The GAIN Study

To define the role of increased fundus autofluorescence (FAF), a surrogate for lipofuscin content, as a risk factor for progression of geographic atrophy (GA). Prospective natural history cohort study, the GAIN (Characterization of geographic atrophy progression in patients with age-related macular degeneration). setting: Single-center study conducted in Barcelona, Spain. After screening of 211 patients, 109 eyes of 82 patients with GA secondary to age-related macular degeneration and a minimum follow-up of 6 months were included. Lipofuscin content was classified independently by 2 masked observers according to FAF patterns described previously. Bivariate, stratified, and multivariable analyses were used to explore the associations between GA growth and independent variables. Mediation analysis was used to evaluate the contribution of FAF patterns to GA progression. Progression of GA in mm(2)/year as measured with FAF. Median follow-up was 18 months (range, 6-42). Median GA growth was 1.61 mm(2)/year. FAF, baseline area of atrophy, and time of follow-up were independently associated with GA progression (P < .004). FAF patterns and baseline area of atrophy were strongly associated (P < .0001), suggesting potential confounding. Mediation analysis suggested that most of the effect of FAF patterns on GA growth was actually caused by baseline area of atrophy. FAF patterns, baseline area of atrophy, and time of follow-up were associated with GA progression. However, FAF patterns seem to be a consequence (not a cause) of enlarging atrophy and their effect on GA progression seems mostly driven by baseline area of atrophy.

Increased Fundus Autofluorescence Related to Outer Retinal Disruption

Increased Fundus Autofluorescence Related to Outer Retinal Disruption

Novel interpretation of fundus autofluorescence (FAF) findings in choriocapillaritis

AbstractPurpose To determine the significance of increased fundus autofluorescence (FAF488) in choriocapillaritis, comparing photobleaching process, SD‐OCT and melanin‐related fundus autofluorescence (FAF787) findingsMethods FAF488 signal depends on both the amount of bisretinoids in the RPE and the absorbion of light by photoreceptor pigments, macular pigment and RPE melanin. During the photobleaching process (absorbion of photons by photopigment in the outer photoreceptor segments), there is a reduction of the photopigment density and so an increase of the visualization of the autofluorescent signalResults In MEWDS and MFC, the more striking FAF488 alteration is an increase of the autofluorescent signal and SD‐OCT shows a disruption of IS/OS junction, probably sign of dismanting outer photoreceptor segments; there is not an increase of FAF787 and after the photobleaching process, the areas of increased FAF488 become isofluorescent. This could mean that the areas of hyperautofluorescence are due to a better visualization of the autofluorescent signal because there is a reduction of the visual pigments and not to an increase of the fluorophores. In the APMPPE group, during the convalescent stage, increased FAF488 and FAF787 are often seen in the center of chorioretinal scars, corresponding to accumulation of fuorophores debris and to hypertrophy/hyperplasia of RPE cellsConclusion In MEWDS and MFC, photobleaching process, FAF787 and spectral‐domain OCT findings may explain the increased FAF488 present in the acute phase of the diseases as a loss of the photopigments and not to an increase of fluorophores, because there is a limited pertubation of choriocapillaris circulation with a slight ischaemic insult to outer retina.

Markers of disease progression in atrophic AMD

AbstractGeographic Atrophy (GA) is a common cause for severe visual loss in age‐related macular degeneration (AMD). In contrast to neovascular AMD in which efficient therapy is now available with intravitreally administered inhibitors of VEGF, there is as yet no therapy available for patients with GA. Natural history studies have demonstrated a continuous progression of outer retinal atrophy in patients with GA. Hereby, a high interindividual variability has been documented with regard to enlargement rates of GA ptaches over time. Various markers of disease progression have been identified including phenotypic charatersitcs on fundus photographs such as soft drusen and hyperpigmentary changes. Furthermore, certain abnormal patterns of increased fundus autofluorescence (FAF) on confocal SLO images have been shown to represent risk characteristics for GA evolution and aloow disrimintaion of slow vs. fast progressors. The status of the fellow also has an imapct on progression rates. SD‐OCT imaging is currently evaluated in ongoing longitudinal studies with respect to specific microstructural alterations in the junctional zone of GA and their impactz for future progression. Idenfication of progrnostic markers is not o9nly important for a better understandibng of the disease process, but also for the design and conduct of interventional clinical trials in patients with GA as enrichment for fast progressors allows to perform such trials in an acceptable time period in a relatively slowly progressing disease, to reduce costs for clinical developments and to increase the likelyhood for the identification of a therapeutic signal.

FOVEAL CAVITATION AS AN OPTICAL COHERENCE TOMOGRAPHY FINDING IN CENTRAL CONE DYSFUNCTION

To describe a distinctive foveal cavitation as seen by spectral-domain optical coherence tomography in certain cone dysfunction syndromes. Observational case series. Patients were evaluated by dilated fundus examination, fundus photography, fundus autofluorescence, full-field electroretinogram, multifocal electroretinogram, spectral-domain optical coherence tomography, color vision testing, fluorescein angiography, Goldmann visual field testing, and molecular genetic analysis. We present eight patients with foveal cavitation in association with presumed cone dysfunction. This was characterized on spectral-domain optical coherence tomography by a gap in the subfoveal outer segment layer without more diffuse retinal thinning. There were 5 patients of age 10 years to 27 years and 3 patients of age 49 years to 52 years, with a 1.5- to 38-year history of bilateral visual loss. A small foveal oval-shaped area of reduced foveal fundus autofluorescence, surrounded by increased fundus autofluorescence, was seen in the younger patients, and a broad circle of increased fundus autofluorescence in the older patients. The multifocal electroretinogram always showed central amplitude reduction, but there were varying degrees of cone dysfunction on full-field electroretinogram. There were mild abnormalities on desaturated color vision testing. The family history was noncontributory in all cases. None of the cases were congenital. ABCA4 gene mutations were identified in three of five patients tested; CNGB3 testing was negative in these patients. Cone dysfunction syndromes typically show retinal thinning on optical coherence tomography imaging, although several case reports have noted focal outer retinal loss. Our case series shows that a distinctive optical coherence tomography finding, foveal cavitation, may be a clue to cone dysfunction syndromes, but is not specific to any one hereditary disorder or age group.

CORRELATION OF INCREASED FUNDUS AUTOFLUORESCENCE SIGNALS AT CLOSED MACULA WITH VISUAL PROGNOSIS AFTER SUCCESSFUL MACULAR HOLE SURGERY

To study the significance of the increased fundus autofluorescence (FAF) signals at closed macula with spectral-domain optical coherence tomography and visual prognosis after successful surgery in eyes with idiopathic full-thickness macular holes (MHs). Seventy-eight eyes of 78 consecutive patients with full-thickness MHs underwent successful standard vitrectomy, with internal limiting membrane peeling and followed by 10% sulfur hexafluoride gas injection. Simultaneous FAF and optical coherence tomography images were recorded at 10 days, and 1, 3, and 6 months postoperatively, using a combined spectral-domain optical coherence tomography-fluorescein angiography device (Spectralis™/HRA Heidelberg Retina Angiograph 2). The appearance of increased FAF in the macula postoperatively and the relationship of FAF and optical coherence tomography findings to best-corrected visual acuity were examined. Stage 2, 3, and 4 MHs were present in 31, 29, and 18 eyes, respectively. The median patient age was 66 years, with a range of 54 to 79 years. In all patients, the MHs were successfully closed, and the preoperative increased FAF corresponding to MH disappeared 10 days after surgery. In 36 eyes (46.2%), however, hyperautofluorescence again appeared in the macular area 1 month postoperatively. This hyperautofluorescence was significantly associated with the recovery of the external limiting membrane lines at the fovea 1 month after surgery (P = 0.001, multiple logistic regression analysis). Also, this recovery of the external limiting membrane lines 1 month postoperatively was significantly associated with the recovery of photoreceptor inner and outer segment junction line 3 months postoperatively at the fovea (P < 0.001, Fisher exact test). Moreover, a good best-corrected visual acuity of 20/28 or better at 6 months after surgery was significantly associated with hyperautofluorescence in the macula 1 month postoperatively, the recovery of the photoreceptor inner and outer segment lines at the fovea 3 months postoperatively, and preoperative good visual acuity (P < 0.05, multiple logistic regression analysis). In full-thickness MHs, 46.2% of our patients showed increased FAF in the macula 1 month after successful MH surgery. This hyperautofluorescence could be a sign of good visual prognosis postoperatively.

SERIAL IMAGING AND STRUCTURE-FUNCTION CORRELATES OF HIGH-DENSITY RINGS OF FUNDUS AUTOFLUORESCENCE IN RETINITIS PIGMENTOSA

To document the evolution and functional and structural significance of parafoveal rings of high-density fundus autofluorescence (AF) in patients with retinitis pigmentosa and preserved visual acuity. Fifty-two patients with nonsyndromic retinitis pigmentosa or Usher syndrome, who had a parafoveal ring of high-density AF and a visual acuity of 20/30 or better, were ascertained. All had international standard full-field electroretinography and pattern electroretinography. Autofluorescence imaging was repeated in 30 patients after periods of up to 9.3 years. Of the 52 patients, 35 underwent optical coherence tomography. Progressive constriction of the ring was detected in 17 patients. Ring radius reduced by up to 40% at a mean rate of between 0.8% and 15.8% per year. In 1 patient, a small ring was replaced by irregular AF; visual acuity deteriorated over the same period. There was a high correspondence between the lateral extent of the preserved optical coherence tomography inner segment/outer segment band and the diameter of the ring along the same optical coherence tomographic scan plane (slope, 0.9; r = 0.97; P < 0.005; n = 35) and between preserved inner segment/outer segment lamina and the pattern electroretinography P50 measure of macular function (R = 0.72; P < 0.005; n = 34). Rings of increased AF surround areas of preserved outer retina and preserved photopic function. Serial fundus AF may provide prognostic indicators for preservation of central acuity and potentially assist in the identification and evaluation of patients suitable for treatment aimed at preservation of remaining function.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IN ADULT-ONSET VITELLIFORM MACULAR DYSTROPHY WITH CUTICULAR DRUSEN

The purpose of this study was to investigate morphologic differences in a consecutive case series of patients suffering from adult-onset vitelliform macular dystrophy with cuticular drusen (CD) compared with another patient group with a vitelliform lesion only using high-resolution in vivo retinal imaging. Simultaneous spectral domain optical coherence tomography (870 nm, 40.000 A-scans per second) and confocal scanning laser ophthalmoscopy were performed in 6 patients (12 eyes) with adult-onset vitelliform macular dystrophy using a combined instrument (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany). Mean age was 69 years (59-82 years), and mean visual acuity was 20/80. The vitelliform lesion presented with an accumulation of yellow-gray material with increased fundus autofluorescence. Spectral domain optical coherence tomography imaging showed that the neurosensory detachment was filled with an amorphous homogenously reflective material located between the retinal pigment epithelium and neurosensory retina in the inferior part of the lesion with the superior part being optically empty. The retinal pigment epithelium basal membrane/Bruch membrane band on spectral domain optical coherence tomography showed multiple focal nodules, in analogy to histologic descriptions of CD. Longitudinal observations in a subgroup of patients showed that the vitelliform detachment collapsed with subsequent development of geographic atrophy in patients with CDs. Cuticular drusen may be an indicator for a generalized retinal pigment epithelium dysfunction. High-resolution spectral domain optical coherence tomography allows to image morphologic differences in adult-onset vitelliform macular dystrophy with and without CDs, providing further evidence that adult-onset vitelliform macular dystrophy with CDs represents a separate disease entity.

Increased Fundus Autofluorescence Associated with Outer Segment Shortening in Macular Translocation Model of Neovascular Age-Related Macular Degeneration

To report the frequency and origins of increased fundus autofluorescence (AF) in age-related macular degeneration using the model of macular translocation. In this retrospective observational case series, postoperative serial fundus AF images from 40 consecutive patients were examined. The origin of well-delineated increased AF changes was explored by examining simultaneous spectral-domain optical coherence tomography (SD-OCT) scans and coregistered microperimetry. AF images were taken between a mean of 13 and 36 months. Seven patients were excluded from analysis because of lack of postoperative AF imaging or extensive macular RPE atrophy. Of the remaining patients, 9 had masking pattern of foveal AF, 21 had small, round increased AF lesions in the fovea, and 3 had a near normal pattern of foveal hypo-AF. Parafoveal increased AF was seen in all 33 patients in 1 of 3 patterns: well-delineated homogenous increased AF patches (17), curvilinear increased AF bands (4), and speckled increased AF (12). Simultaneous SD-OCT showed loss of signal from the interface of the inner and outer segments of the photoreceptor cell layer with variable loss of outer nuclear layer thickness. Microperimetry showed subnormal retinal sensitivity in regions with increased AF. Parafoveal increased AF size remained stable for 2 to 5 years of follow-up. SD-OCT and microperimetry changes observed after translocation may be attributed to shortening of the outer segments. A corresponding reduction of visual pigment in the shortened outer segments may lead to an unmasking effect. Increased AF in some macular diseases may be attributed to unmasking of AF rather than to increased fluorophores within abnormal retina.

Fundus Autofluorescence and Progression of Age-related Macular Degeneration

Fundus autofluorescence imaging is an imaging method that provides additional information compared to conventional imaging techniques. It permits to topographically map lipofuscin distribution of the retinal pigment epithelial cell monolayer. Excessive accumulation of lipofuscin granules in the lysosomal compartment of retinal pigment epithelium cells represents a common downstream pathogenetic pathway in various hereditary and complex retinal diseases including age-related macular degeneration (AMD). This comprehensive review contains an introduction in fundus autofluorescence imaging, including basic considerations, the origin of the signal, different imaging methods, and a brief overview of fundus autofluorescence findings in normal subjects. Furthermore, it summarizes cross-sectional and longitudinal fundus autofluorescence findings in patients with AMD, addresses the pathophysiological significance of increased fundus autofluorescence, and characterizes different fundus autofluorescence phenotypes as well as fundus autofluorescence alterations with disease progression.

Discrete arcs of increased fundus autofluorescence in retinal dystrophies and functional correlate on microperimetry

To describe the occurrence of discrete arcs of increased fundus autofluorescence (FAF) associated with various retinal dystrophies and to assess their functional significance by fundus-controlled microperimetry. Seven patients, three with pigmented paravenous retinochoroidal atrophy (PPRCA), one with sector retinitis pigmentosa (RP), one with typical RP, and two with macular dystrophy were assessed by retinal imaging including FAF imaging. Serial images were obtained within a review period of 6 and 10 years in a patient with PPRCA and macular dystrophy, respectively. Fundus-controlled microperimetry was performed in eight eyes of five patients to determine light increment sensitivity. A discrete arched line of increased FAF was observed without obvious correlate on fundus biomicroscopy. The orientation of this line differed from ring shape in RP and macular dystrophy, a semi-circle structure in sector RP to crescent shape with tiplike extensions towards branching retinal veins in PPRCA. Longitudinal investigation revealed slight migration of the arc in PPRCA and peripheral extension of the ring diameter in macular dystrophy. Microperimetry revealed that the arc of increased FAF sharply delineated areas of severely impaired retinal sensitivity. The findings indicate that arcs of increased FAF in PPRCA and other retinal dystrophies demarcate areas of impaired retinal function and may migrate over time. FAF imaging may therefore reveal the exact extent of neurosensory dysfunction that may exceed the dimensions anticipated by conventional examinations.