Retinal Pigment Epithelium Abnormalities Research Articles

Questioning photostasis

Photostasis is a phenomenon where the photoreceptor outer segment (OS) length and its rhodopsin content vary depending on environmental lighting. When light is reduced for extended periods, it is argued that OS lengthen and its rhodopsin concentration rises to increase photon capture in darker environment. Increases in OS length may occur because the retinal pigment epithelium (RPE) cells reduce OS consumption in prolonged darkness. But sample sizes in assessing changes in OS length have been small, and results highly varied with no statistical analysis ever offered. Further, animals used were often albinos, which have abnormal RPE cells. Here we keep pigmented and albino mice for 21 days in darkness and compare OS length with those in a normal 12:12 light/dark environment. We measured approximately 1300 OS but found no statistically significant difference in their lengths between light and dark groups in either pigmentation phenotype, although there was a small trend in the data favoring OS extension in the dark. Given that earlier studies were undertaken on limited samples with no statistical analysis, our data pose serious questions for the notion of mammalian photostasis in terms of significant OS plasticity.

Multifocal electroretinographic evaluation of macular function in acute posterior multifocal placoid pigment epitheliopathy

In acute posterior multifocal placoid pigment epitheliopathy (APMPPE), little is known about the long-term outcome of electroretinographic macular function. The purpose of this study was to report 2-year follow-up results of multifocal electroretinography (mfERG) in a 26-year-old Japanese woman diagnosed with APMPPE. Clinical and electrophysiological investigations of a single patient. Best-corrected visual acuity at initial examination was 1.5 and 0.5 in her right and left eyes, respectively. In addition to characteristic fundus lesions bilaterally, fluorescein angiography demonstrated diagnostic early blockage and late staining of the lesions. Optical coherence tomography revealed a hyperreflective spot (corresponding to the lesion) in the outer retinal layer in the right eye and intraretinal fluid in the left eye. On mfERG, the amplitudes were generally preserved, but markedly reduced amplitudes were detected in the central region of the left eye and in the paracentral region of the right eye. Five days later, visual acuity improved to 1.0, and the intraretinal fluid spontaneously disappeared without medication in the left eye. Light-to-dark ratios on electrooculography were 2.68 and 2.23 in the right and left eyes, respectively, both within the normal range. Two years later, visual acuity was 2.0 in both eyes, and ophthalmoscopically, there were neither retinal nor retinal pigment epithelial (RPE) abnormalities. mfERG revealed that the amplitudes were considerably improved (nearly normal level) in both eyes. The outcome suggests that longitudinal macular function in both visual acuity and mfERG may be favorable, unless areas of retinal or RPE alteration remain.

Correlation between peripapillary retinal nerve fiber layer thickness and fundus autofluorescence in primary open-angle glaucoma

PurposeTo investigate the relationship between retinal nerve fiber layer (RNFL) thickness and retinal pigment epithelium alterations in patients with advanced glaucomatous visual field defects.MethodsA consecutive, prospective series of 82 study eyes with primary open-angle glaucoma and advanced glaucomatous visual field defects were included in this study. All study participants underwent a full ophthalmic examination followed by visual field testing with standard automated perimetry as well as spectral-domain optical coherence tomography (SD-OCT) for peripapillary RNFL thickness and Optos wide-field fundus autofluorescence (FAF) images. A pattern grid with corresponding locations between functional visual field sectors and structural peripapillary RNFL thickness was aligned to the FAF images at corresponding location. Mean FAF intensity (range: 0 = black and 255 = white) of each evaluated sector (superotemporal, temporal, inferotemporal, inferonasal, nasal, superonasal) was correlated with the corresponding peripapillary RNFL thickness obtained with SD-OCT.ResultsCorrelation analyses between sectoral RNFL thickness and standardized FAF intensity in the corresponding topographic retina segments revealed partly significant correlations with correlation coefficients ranging between 0.004 and 0.376 and were statistically significant in the temporal inferior central field (r = 0.324, P = 0.036) and the nasal field (r = 0.376, P = 0.014).ConclusionRetinal pigment epithelium abnormalities correlate with corresponding peripapillary RNFL damage, especially in the temporal inferior sector of patients with advanced glaucomatous visual field defects. A further evaluation of FAF as a potential predictive parameter for glaucomatous damage is necessary.

Lipofuscin- and melanin-related fundus autofluorescence in patients with submacular idiopathic choroidal neovascularization.

To compare melanin-related near-infrared fundus autofluorescence (NIA; excitation 787 nm, emission> 800 nm) with lipofuscin-related fundus autofluorescence (FAF; excitation 488 nm, emission > 500 nm) in patients with idiopathic choroidal neovascularization (ICNV). FAF, NIA, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were obtained using a confocal scanning laser Ophthalmoscope HRA2 (Heidelberg Retina Angiograph 2) in 18 eyes of 18 patients with ICNV. Eighteen eyes had classic CNV, and autofluorescence imaging showed hypoautofluorescence at the site of CNV. A well-defined hyperautofluorescent ring was detected surrounding the CNV in all 18 eyes with NIA imaging. In our sample, the FAF patterns around the CNV were classified as normal (n=1, 5.56%), well-defined hyperautofluorescent ring (n=7, 38.89%), or ill-defined hyperautofluorescent ring (n=10, 55.56%). The patterns of FAF and NIA indicated different involvement of lipofuscin and melanin in the pathophysiological process of ICNV. Compared to FAF imaging, NIA imaging appears to be a superior noninvasive method for in vivo visualization of retinal pigment epithelium (RPE) abnormalities in ICNV patients.

RANDOMIZED CLINICAL TRIAL FRANCE DMLA2

To evaluate the effect of trimetazidine (TMZ) in a randomized, double-blind, placebo-controlled clinical trial on the occurrence of choroidal neovascularization or geographic atrophy in age-related macular degeneration. A total of 1,086 patients from France, Belgium, and Spain with soft drusen and/or retinal pigment epithelium abnormalities in the study eye and choroidal neovascularization in the contralateral eye were randomly assigned to receive orally placebo or TMZ 70 mg daily (35 mg × 2) and followed-up for 3 years to 5 years. Treatment duration ranged between 0.4 months and 67.8 months with a mean ± SD of 38 ± 16 months. Three hundred and fifty-eight patients developed choroidal neovascularization (incidence per 100 patient-years: TMZ 10.86; placebo 11.13). Trimetazidine did not prevent the choroidal neovascularization (hazard ratio = 0.97; 95% confidence interval, 0.77-1.20; P = 0.781). However, there was a trend favoring TMZ for retinal atrophy, a secondary endpoint (HR = 0.76; 95% confidence interval, 0.56-1.02; P = 0.069). Overall, the difference in atrophy incidence between TMZ and placebo was not statistically different. Differences within some prespecified subgroups of patients showed superiority of TMZ in men (HR = 0.50; 95% confidence interval, 0.28-0.89; p = 0.016), in patients aged ≤75 years (HR = 0.58; 95% confidence interval, 0.38-0.88; p = 0.010), or in patients presenting with isolated pigmentary changes (HR = 0.19; 95% confidence interval, 0.05-0.70; p = 0.005). Trimetazidine failed to prevent choroidal neovascularization. Subgroup analyses suggest that this drug could be tested as preventive therapy for geographic atrophy, although the overall comparison showed no statistically significant differences in the progression of geographic atrophy.

Anti-inflammatory recombinant TSG-6 stabilizes the progression of focal retinal degeneration in a murine model

BackgroundInflammatory responses are detected in the retina of patients with age-related macular degeneration and Ccl2-/-/Cx3cr1-/- mice on rd8 background,(Ccl2-/-/Cx3cr1-/- mice) a model that develops progressive age-related macular degeneration-like retinal lesions including focal photoreceptor degeneration, abnormal retinal pigment epithelium and A2E accumulation. Tumor necrosis factor-inducible gene 6 protein is an anti-inflammatory protein and has been shown to improve myocardial infarction outcome and chemically injured cornea in mice by suppressing inflammation. In this study, we evaluated the effect of an intravitreous injection of recombinant TSG-6 on the retinal lesions of Ccl2-/-/Cx3cr1-/- mice.MethodsRecombinant TSG-6 (400 ng) was administered by intravitreous injection into the right eye of six-week-old Ccl2-/-/Cx3cr1-/- mice. Their left eye was injected with phosphate-buffered saline as a control. Funduscopic pictures were taken before injection and sequentially once a month after injection. The mice were killed two months after injection and the ocular histology examined. Retinal A2E, a major component of lipofuscin, was measured by high performance liquid chromatography. The microarray of ocular mRNA of 92 immunological genes was performed. The genes showing differentiated expression in microarray were further compared between the injected right eye and the contralateral (control) eye by [real-time quantitative reverse transcription polymerase chain reaction] qRT-PCR.ResultsThe continuous monitoring of the fundus for two months showed a slower progression or alleviation of retinal lesions in the treated right eyes as compared with the untreated left eyes. Among 23 pairs of eyes, the lesion levels improved in 78.3%, stayed the same in 8.7% and progressed in 13.0%. Histology confirmed the clinical observation. Even though there was no difference in the level of A2E between the treated and the untreated eyes, microarray analysis of 92 immune genes showed that IL-17a was substantially decreased after the treatment. Expression of TNF-α showed a similar pattern to IL-17a. The results were consistent in duplicated arrays and confirmed by qRT-PCR.ConclusionsWe concluded that intravitreous administration of recombinant TSG-6 might stabilize retinal lesions in Ccl2-/-/Cx3cr1-/- mice on rd8 background. Modulation of ocular immunological gene expressions, especially IL-17a, could be one of the mechanisms.

Genetics of Immunological and Inflammatory Components in Age-related Macular Degeneration

Age-related macular degeneration (AMD), affecting 30 to 50 million elder individuals worldwide, is a disease affecting the macular retina and choroid that can lead to irreversible central vision loss and blindness. Recent findings support a role for immunologic processes in AMD pathogenesis, including generation of inflammatory related molecules in the Bruch’s membrane, recruitment of macrophages, complement activation, microglial activation and accumulation in the macular lesions. Pro-inflammatory effects of chronic inflammation and oxidative stress can result in abnormal retinal pigment epithelium, photoreceptor atrophy and choroidal neovascularization. The associations of immunological and inflammatory genes, in particular the genes related to innate immunity with AMD support the involvement of various immunological pathways in the AMD pathogenesis. We review the literature on the involvements of inflammatory genes in AMD, highlight recent genetic discoveries, and discuss the potential application of such knowledge in the management of patients with AMD.

Morphologic Changes in Acute Central Serous Chorioretinopathy Using Spectral Domain Optical Coherence Tomography

PurposeTo investigate morphologic changes of acute central serous chorioretinopathy (CSC) using spectral domain optical coherence tomography (SD-OCT) and confocal scanning laser ophthalmoscopy.MethodsThis retrospective study included 63 eyes of 63 patients with unilateral acute CSC. All patients underwent simultaneous SD-OCT and fluorescein angiography examination using Spectralis HRA+OCT.ResultsThe external limiting membrane could be seen on SD-OCT, although the junction between photoreceptor inner and outer segments (IS/OS) was not detected in all eyes with retinal detachment (RD). However, IS/OS became visible after resolution of serous RD in 51 eyes (81.0%). SD-OCT images at the leakage sites showed a bump of retinal pigment epithelium (RPE) in in 47 cases (68.1%) and pigment epithelial detachment (PED) in 22 of 69 leakage sites (31.9%). In 14 of 69 leakage sites (20.3%), highly reflective areas suggesting fibrinous exudate were observed in the subretinal space. In nine leakage sites (13.0%), sagging or dipping of the posterior retinal layer was seen. Abnormal RPE changes such as RPE bump and PED were observed in 12 of 22 fellow eyes (54.5%).ConclusionsA variety of morphologic changes could be identified on SD-OCT, and those findings may contribute more information to our understanding of the pathophysiology of CSC.

Congenital Ocular Anomaly in an Infant with Trisomy 14 Mosaicism

Trisomy 14 mosaicism is a rare chromosomal abnormality with distinct and recognizable clinical features. We report a patient with presumed retinal dystrophy having diffuse retinal pigment epithelial abnormalities, which has not been previously reported in association with trisomy 14. This case expands the clinical spectrum of this rare entity.

PALS1 Is Essential for Retinal Pigment Epithelium Structure and Neural Retina Stratification

The membrane-associated palmitoylated protein 5 (MPP5 or PALS1) is thought to organize intracellular PALS1-CRB-MUPP1 protein scaffolds in the retina that are involved in maintenance of photoreceptor-Müller glia cell adhesion. In humans, the Crumbs homolog 1 (CRB1) gene is mutated in progressive types of autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. However, there is no clear genotype-phenotype correlation for CRB1 mutations, which suggests that other components of the CRB complex may influence the severity of retinal disease. Therefore, to understand the physiological role of the Crumbs complex proteins, especially PALS1, we generated and analyzed conditional knockdown mice for Pals1. Small irregularly shaped spots were detected throughout the PALS1 deficient retina by confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography. The electroretinography a- and b-wave was severely attenuated in the aged mutant retinas, suggesting progressive degeneration of photoreceptors. The histological analysis showed abnormal retinal pigment epithelium structure, ectopic photoreceptor nuclei in the subretinal space, an irregular outer limiting membrane, half rosettes of photoreceptors in the outer plexiform layer, and a thinner photoreceptor synaptic layer suggesting improper photoreceptor cell layering during retinal development. The PALS1 deficient retinas showed reduced levels of Crumbs complex proteins adjacent to adherens junctions, upregulation of glial fibrillary acidic protein indicative of gliosis, and persisting programmed cell death after retinal maturation. The phenotype suggests important functions of PALS1 in the retinal pigment epithelium in addition to the neural retina.

Features of frequency domain optical coherence tomography in acute central serous chorioretinopathy

Objective To observe the features of frequency domain optical coherence tomography (FD-OCT) in acute central serous chorioretinopathy (CSC).Methods The data of FD-OCT and fundus fluorescein angiography (FFA) of 31 patients with unilateral acute CSC were retrospectively analyzed.The FD-OCT of retinal pigment epithelial (RPE) layer at leakage points, retinal detachment area and RPE layer in the fellow eyes was documented.Results Thirty-four leakage points were detected in 31 eyes on FFA.At the sites of fluorescein leakage, FD-OCT showed that serous pigment epithelial detachment (PED) in 18leakage points (52.9%) and 17 eyes (54.8%), a small RPE protrusion in 8 leakage points (23.5%) and 8eyes (25.8%), RPE irregularity in 6 leakage points (17.6%) and 4 eyes (12.9%) and no detectable RPE abnormality in 2 leakage points (5.9%) and 2 eyes (6.5%).An RPE defect at the edge of or within the fPED was found in 7 leakage points (20.6%) and 7 eyes (22.6%).Serous retinal detachment and interruption or complete disappearance of the hyper-reflective inner/outer segment junction (IS/OS) were detected in all diseased eyes.Uneven thickness of the outer segments (OS) was found in 24 eyes (77.4%),14 of which had sagging sign.Flaking of the OS was found in 10 eyes (32.3%), multiple hyper-reflective dots on the posterior surface of the detached neurosensory retina and on the surface of the RPE were found in 8 eyes (25.8%).Among 31 fellow eyes, FD-OCT also showed RPE abnormalities in 11 eyes (35.5%),in which PED, RPE protrusion and RPE irregularity were detected in 2 (6.5%), 1 (3.2%) and 8 eyes (25.8%), respectively.Conclusions In acute CSC the FD-OCT images at leakage points of are featured by PED, RPE protrusion, RPE irregularity and no detectable RPE abnormality; in retinal detachment area FD-OCT are featured by serous retinal detachment, interruption or disappearance of IS/OS, uneven thickness of OS, flaking of OS and hyper-reflective dots on the posterior surface of the detached neurosensory retina and on the surface of the RPE. Key words: Retinal diseases/ diagnosis; Choroid diseases/ diagnosis; Pigment epithelium of eye; Tomography, optical coherence; Diagnostic imaging

A CTRP5 gene S163R mutation knock-in mouse model for late-onset retinal degeneration

Late-onset retinal macular degeneration (L-ORD) is an autosomal dominant inherited disorder caused by a single missense mutation (S163R) in the CTRP5/C1QTNF5 protein. Early phenotypic features of L-ORD include: dark adaptation abnormalities, nyctalopia, and drusen deposits in the peripheral macular region. Apart from posterior segment abnormalities, these patients also develop abnormally long anterior lens zonules. In the sixth decade of life the rod and cone function declines, accompanied by electroretinogram (ERG) abnormalities. Some patients also develop choroidal neovascularization and glaucoma. In order to understand the disease pathology and mechanisms involved in retinal dystrophy, we generated a knock-in (Ctrp5(+/-)) mouse model carrying the disease-associated mutation in the mouse Ctrp5/C1QTNF5 gene. These mice develop slower rod-b wave recovery consistent with early dark adaptation abnormalities, accumulation of hyperautofluorescence spots, retinal pigment epithelium abnormalities, drusen, Bruch's membrane abnormalities, loss of photoreceptors, and retinal vascular leakage. The Ctrp5(+/-) mice, which have most of the pathological features of age-related macular degeneration, are unique and may serve as a valuable model both to understand the molecular pathology of late-onset retinal degeneration and to evaluate therapies.

Impact of early and late age-related macular degeneration on vision-specific functioning

AimTo assess the impact of early and late age-related macular degeneration (AMD) on vision-specific functioning in Singapore Malays.MethodsAMD was assessed from fundus photographs. The following endpoints were considered for (a)...

Characteristics of Patients Losing Vision after 2 Years of Monthly Dosing in the Phase III Ranibizumab Clinical Trials

To investigate the cause of visual acuity (VA) loss in patients with neovascular age-related macular degeneration (AMD) receiving monthly ranibizumab injections in the pivotal ranibizumab phase III trials. Retrospective analysis. The Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab In the treatment of Neovascular AMD (MARINA) and Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD (ANCHOR) trials. Demographics and lesion characteristics at baseline and month 24 were compared in patients with ≥15 letters VA loss and patients with ≥15 letters VA gain from baseline to month 24. Additional evaluations of fundus photographs from these patients were performed to assess features of non-exudative AMD, such as geographic atrophy (GA) and retinal pigment epithelium (RPE) abnormalities. Differences in lesion characteristics between patients who lost versus gained ≥15 letters of VA from baseline to month 24. At month 24, 9% of ranibizumab-treated patients from MARINA and 10% of ranibizumab-treated patients from ANCHOR had lost ≥15 letters VA; 30% of ranibizumab-treated patients from MARINA and 38% of ranibizumab-treated patients from ANCHOR had gained ≥15 letters VA. Baseline characteristics associated with VA loss at month 24 included older age, better VA, and larger lesions. At month 24, an increased area of RPE abnormality was associated with VA loss in both the MARINA (P = 0.0008) and ANCHOR (P = 0.0046) trials. Increased total lesion area at month 24 was associated with VA loss in both trials. In MARINA, the increase in total lesion area was attributable to an increase in the angiographic designation of atrophic scar among VA losers (P = 0.0043), but in ANCHOR it was attributable to an increased area of choroidal neovascularization (CNV) (P = 0.039) but not an increased area of leakage (P = 0.17). Increased areas of GA, fibrosis, and hemorrhage were not associated with VA loss. Vision loss after 2 years of monthly ranibizumab therapy was associated with lesion characteristics commonly associated with suppressed CNV, such as pigmentary abnormalities, atrophic scar, and the absence of leakage. Future VA improvements in patients receiving ranibizumab therapy may require preservation of photoreceptor and RPE function rather than strategies that target CNV.

The Impact of Fish and Shellfish Consumption on Age-Related Macular Degeneration

To determine the relationship between fish and shellfish consumption and age-related macular degeneration (AMD) status in the Salisbury Eye Evaluation (SEE) Study participants. A cross-sectional study of dietary and ophthalmologic data. A random sample of 2520 Salisbury, Maryland, residents aged 65 to 84 years. A food frequency questionnaire was used to estimate weekly fish/shellfish consumption for each participant. Age-related macular degeneration status was determined from fundus photographs obtained at baseline and graded by 2 masked readers for drusen size, retinal pigment epithelium abnormalities, geographic atrophy (GA), and choroidal neovascularization (CNV). The association between weekly fish/shellfish intake and risk of AMD was investigated using logistic regression while adjusting for risk factors and correlation between eyes. Status of AMD. The distribution of weekly fish/shellfish consumption was not different between specific AMD categories compared with controls (P = 0.6, 0.7, and 0.7 for large drusen, pigment abnormalities, and advanced AMD compared with controls, respectively). Those with advanced AMD (CNV or GA) were significantly less likely to consume fish/shellfish high in omega-3 fatty acids (odds ratio 0.4; confidence interval, 0.2-0.8). There was no relationship of AMD with intake of crab and oysters combined, each of which has high levels of zinc. These data support a protective effect of fish/shellfish intake against advanced AMD.

Blue light and near-infrared fundus autofluorescence in acute Vogt–Koyanagi–Harada disease

Background/aimsTo investigate the characteristics of fundus autofluorescence (FAF) in acute Vogt–Koyanagi–Harada (VKH) disease.MethodsFAF photography with blue light (BL-FAF) and near-infrared light (NIR-FAF) was performed on 10 eyes of five patients...

An essential role for RPE-derived soluble VEGF in the maintenance of the choriocapillaris

Clinical and experimental observations indicate a role for VEGF secreted by the retinal pigment epithelium (RPE) in the maintenance of the choriocapillaris (CC). VEGF in mice is produced as three isoforms, VEGF120, VEGF164, and VEGF188, that differ in their ability to bind heparan sulfate proteoglycan. RPE normally produces the more soluble isoforms, VEGF120 and VEGF164, but virtually no VEGF188, reflecting the fact that molecules secreted by the RPE must diffuse across Bruch's membrane (BrM) to reach the choriocapillaris. To determine the role of RPE-derived soluble VEGF on the choriocapillaris survival, we used mice that produce only VEGF188. VEGF188/188 mice exhibited normal choriocapillaris development. However, beginning at 7 months of age, we observed a progressive degeneration characterized by choriocapillaris atrophy, RPE and BrM abnormalities, culminating in areas of RPE loss and dramatic choroidal remodeling. Increased photoreceptor apoptosis in aged VEGF188/188 mice led to a decline in visual acuity as detected by electroretinogram (ERG). These changes are reminiscent of geographic atrophy (GA) and point to a role for RPE-derived VEGF in the maintenance of the choriocapillaris.

Torpedo maculopathy

AimTo describe the fluorescein angiographic, fundus autofluorescence and optical coherence tomography (OCT) findings in patients with a unique unilateral lesion of the temporal macula previously named torpedo maculopathy.MethodThis study was...

A High Omega-3 Fatty Acid Diet Reduces Retinal Lesions in a Murine Model of Macular Degeneration

Age-related macular degeneration (AMD) is one of the leading cause of blindness among the elderly; however, current therapy options are limited. Epidemiological studies have shown that a diet that is high in omega-3 polyunsaturated (n-3) fatty acids can slow disease progression in patients with advanced AMD. In this study, we evaluated the effect of such a diet on the retinas of Ccl2(-/-)/Cx3cr1(-/-) mice, a model that develops AMD-like retinal lesions that include focal deep retinal lesions, abnormal retinal pigment epithelium, photoreceptor degeneration, and A2E accumulation. Ccl2(-/-)/Cx3cr1(-/-) mice that ingested a high n-3 fatty acid diet showed a slower progression of retinal lesions compared with the low n-3 fatty acids group. Some mice that were given high levels of n-3 fatty acids had lesion reversion. We found a shunted arachidonic acid metabolism that resulted in decreased pro-inflammatory derivatives (prostaglandin E(2) and leukotriene B(4)) and an increased anti-inflammatory derivative (prostaglandin D(2)). We also measured lower ocular TNF-alpha and IL-6 transcript levels in the mice fed a diet of high n-3 fatty acids. Our findings in these mice are in line with human studies of AMD risk reduction by long-chain n-3 fatty acids. This murine model provides a useful tool to evaluate therapies that might delay the development of AMD.

Lipofuscin- and Melanin-related Fundus Autofluorescence in Patients with ABCA4-associated Retinal Dystrophies

To compare melanin-related near-infrared fundus autofluorescence (NIA; excitation 787 nm, emission > 800 nm) to lipofuscin-related fundus autofluorescence (FAF; excitation 488 nm, emission > 500 nm) in patients with retinal dystrophies associated with ABCA4 gene mutations (ABCA4-RD). Observational case series. Sixteen consecutive patients with ABCA4-RD diagnosed in one institution were included. FAF and NIA imaging were performed with a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2; Heidelberg Engineering, Heidelberg, Germany). The pattern and size of retinal pigment epithelial (RPE) alterations detected with FAF and NIA were evaluated. FAF and NIA alterations were detected in all patients. In 7 of 16 patients, the alterations progressed beyond the vascular arcades, and in 9 of 16, they were confined to the macula. Spots of increased NIA (4/16) were less frequent compared with spots of increased FAF (15/16). Confluent patches of reduced NIA were frequent (12/16), and severely reduced NIA was observed in 3 cases. Areas with reduced NIA corresponded to either increased or reduced FAF. Preservation of subfoveal FAF or NIA corresponded to visual acuity > or = 0.4. Abnormalities detected with NIA were more extensive or more severe compared to FAF in 15 of 16 patients. Patterns of FAF and NIA indicate different involvement of lipofuscin and melanin and their derivates in the pathophysiologic process of ABCA4-RD. NIA imaging provides a noninvasive in vivo visualization of RPE abnormalities that may precede FAF alterations during the degenerative process. Combined FAF and NIA imaging will provide further insight in the development of ABCA4-RD and could help to monitor future therapeutic interventions.