Atrophic Atrophic Age-related Macular Degeneration Research Articles

Microperimetry Characteristics of Regions With a Truly Nonresponding Location: Implications for Atrophic Age-Related Macular Degeneration.

To understand the microperimetry response characteristics of regions with a truly nonresponding location, which will be useful when considering criteria for end-stage atrophic age-related macular degeneration (AMD). A simulation model was developed using data from 128 participants with bilateral large drusen at baseline seen over 36months at 6-month intervals. One hundred thousand pairs of real-world microperimetry testing results were simulated separately with and without one truly nonresponding location, where the sensitivity of one randomly selected location for the former group was derived from the distribution of responses from a truly nonresponding location at the optic nerve head from 60 healthy participants. Only 60% of the simulated test pairs with a truly nonresponding location had ≥1 location that was <0 decibel (dB) on both tests. In contrast, 91% of the simulated test pairs had ≥1 location that was ≤10dB on both tests, and 87% had ≥1 location that was ≤10dB on both tests and <0dB for one of the tests. Of the simulated test pairs without a truly nonresponding location, there were 0.04%, 1.4%, and 0.4% that met these three above criteria, respectively. Regions with a truly nonresponding test location do not almost always show a repeatable absolute scotoma (<0dB), but instead, much more often a deep visual sensitivity defect (≤10dB), with or without having an absolute scotoma on one of the tests. These findings are crucial if functional criteria are to be considered as part of a definition of end-stage atrophic AMD.

Simultaneous perception of prosthetic and natural vision in AMD patients

Loss of photoreceptors in atrophic age-related macular degeneration (AMD) results in severe visual impairment. Since the low-resolution peripheral vision is retained in such conditions, restoration of central vision should not jeopardize the surrounding healthy retina and allow for simultaneous use of the natural and prosthetic sight. This interim report, prespecified in the study protocol, presents the first clinical results with a photovoltaic substitute of the photoreceptors providing simultaneous use of the central prosthetic and peripheral natural vision in atrophic AMD. In this open-label single group feasibility trial (NCT03333954, recruitment completed), five patients with geographic atrophy have been implanted with a wireless 2 x 2 mm-wide 30 µm-thick device, having 378 pixels of 100 µm in size. All 5 patients achieved the primary outcome of the study by demonstrating the prosthetic visual perception in the former scotoma. The four patients with a subretinal placement of the chip demonstrated the secondary outcome: Landolt acuity of 1.17 ± 0.13 pixels, corresponding to the Snellen range of 20/460–20/565. With electronic magnification of up to a factor of 8, patients demonstrated prosthetic acuity in the range of 20/63–20/98. Under room lighting conditions, patients could simultaneously use prosthetic central vision and their remaining peripheral vision in the implanted eye and in the fellow eye.

Automated foveal location detection on spectral-domain optical coherence tomography in geographic atrophy patients

PurposeTo develop a fully automated algorithm for accurate detection of fovea location in atrophic age-related macular degeneration (AMD), based on spectral-domain optical coherence tomography (SD-OCT) scans.MethodsImage processing was conducted on a cohort of patients affected by geographic atrophy (GA). SD-OCT images (cube volume) from 55 eyes (51 patients) were extracted and processed with a layer segmentation algorithm to segment Ganglion Cell Layer (GCL) and Inner Plexiform Layer (IPL). Their en face thickness projection was convolved with a 2D Gaussian filter to find the global maximum, which corresponded to the detected fovea. The detection accuracy was evaluated by computing the distance between manual annotation and predicted location.ResultsThe mean total location error was 0.101±0.145mm; the mean error in horizontal and vertical en face axes was 0.064±0.140mm and 0.063±0.060mm, respectively. The mean error for foveal and extrafoveal retinal pigment epithelium and outer retinal atrophy (RORA) was 0.096±0.070mm and 0.107±0.212mm, respectively. Our method obtained a significantly smaller error than the fovea localization algorithm inbuilt in the OCT device (0.313±0.283mm, p <.001) or a method based on the thinnest central retinal thickness (0.843±1.221, p <.001). Significant outliers are depicted with the reliability score of the method.ConclusionDespite retinal anatomical alterations related to GA, the presented algorithm was able to detect the foveal location on SD-OCT cubes with high reliability. Such an algorithm could be useful for studying structural-functional correlations in atrophic AMD and could have further applications in different retinal pathologies.

Optimisation of a Novel Bio-Substrate as a Treatment for Atrophic Age-Related Macular Degeneration.

Atrophic age-related macular degeneration (AMD) is the most common form of AMD accounting for 90% of patients. During atrophic AMD the waste/exchange pathway between the blood supply (choroid) and the retinal pigment epithelium (RPE) is compromised. This results in atrophy and death of the RPE cells and subsequently the photoreceptors leading to central blindness. Although the mechanisms behind AMD are unknown, the growth of fatty deposits known as drusen, have been shown to play a role in the disease. There is currently no treatment or cure for atrophic AMD. Much research focuses on developing a synthetic substrate in order to transplant healthy cells to the native Bruch’s membrane (BM), however, the diseased native BM and related structures still leave potential for transplanted cells to succumb to disease. In this proof-of-concept work we electrospun poly(ethylene terephthalate) (PET) to fabricate a nanofibrous cytocompatible synthetic BM. The apical surface of the membrane was cultured with ARPE-19 cells and the underside was decorated with poly(lactic acid-co-glycolic acid) (PLGA) or poly(glycolic acid) (PGA) degradable nanoparticles by electrospraying. The membrane exhibited hydrophilicity, high tensile strength and structurally resembled the native BM. ARPE-19 cells were able to form a monolayer on the surface of the membrane and no cell invasion into the membrane was seen. The presence of both PLGA and PGA nanoparticles increased ARPE-19 cell metabolism but had no effect on cell viability. There was a decrease in pH of ARPE-19 cell culture media 7 days following culturing with the PLGA nanoparticles but this change was eliminated by 2 weeks; PGA nanoparticles had no effect on cell culture media pH. The fluorescent dye FITC was encapsulated into nanoparticles and showed sustained release from PLGA nanoparticles for 2 weeks and PGA nanoparticles for 1 day. Future work will focus on encapsulating biologically active moieties to target drusen. This could allow this novel bioactive substrate to be a potential treatment for atrophic AMD that would function two-fold: deliver the required monolayer of healthy RPE cells to the macula on a synthetic BM and remove diseased structures within the retina, restoring the waste/exchange pathway and preventing vision loss.

Agreement between ophthalmologists and optometrists in the certification of vision impairment

Background/objectivesThe certification process to register patients as sight impaired or severely sight impaired is undertaken by consultant ophthalmologists, in the UK. We sought to assess the agreement between optometrists and a consensus panel, in identifying patient eligibility for certification, relative to the agreement between ophthalmologists and the consensus panel.MethodsThe consensus panel (4 consultant ophthalmologists and 3 optometrists with a formal accreditation in low vision), 30 consultant ophthalmologists and 99 low vision optometrists reviewed 40 randomly selected abridged cases. The eligibility outcomes from the ophthalmologists and the optometrists were compared with the consensus panel outcomes.ResultsFor ophthalmologists and optometrists, the median (IQR) number of cases in which there was agreement with the consensus panel was 33.0 (31.0, 33.0) and 36.0 (34.0, 36.5), respectively. In severely sight impaired cases, the probabilities of agreeing on eligibility for certification were 76.0% (95% CIs 71.4%, 80.1%) for ophthalmologists and 61.8% (59.0%, 64.6%) for optometrists. In sight impaired cases, the corresponding values were 51.6% (46.7%, 56.4%) for ophthalmologists and 72.2% (69.8%, 74.5%) for optometrists. In cases of bilateral atrophic age-related macular degeneration (AMD), both groups were more likely to agree with the consensus panel and the differences between optometrists and ophthalmologists were less marked.ConclusionsOptometrists demonstrated a comparable agreement relative to ophthalmologists, with the consensus panel on the eligibility of randomly selected, abridged cases for certification. The findings support the clinical decision-making ability of low vision optometrists in the certification of patients with vision impairment and provide evidence in support of policy change to allow low vision optometrists to certify individuals with atrophic AMD.

NA3 glycan: a potential therapy for retinal pigment epithelial deficiency.

Atrophic age-related macular degeneration (AMD) is the most common type of AMD, yet there is no United States Food and Drug Administration (FDA)-approved therapy. This disease is characterized by retinal pigment epithelial (RPE) insufficiency, primarily in the macula, which affects the structure and physiology of photoreceptors and ultimately, visual function. In this study, we evaluated the protective effects of a naturally derived small molecule glycan therapeutic-asialo-, tri-antennary complex-type N-glycan (NA3)-in two distinct preclinical models of atrophic AMD. In RPE-deprived Xenopuslaevis tadpole eyes, NA3 supported normal retinal ultrastructure. In RCS rats, NA3 supported fully functioning visual integrity. Furthermore, structural analyses revealed that NA3 prevented photoreceptor outer segment degeneration, pyknosis of the outer nuclear layer, and reactive gliosis of Müller cells (MCs). It also promoted maturation of adherens junctions between MC and photoreceptors. Our results demonstrate the neuroprotective effects of a naturally derived small molecular glycan therapeutic-NA3-in two unique preclinical models with RPE insufficiency. These data suggest that NA3 glycan therapy may provide a new therapeutic avenue in the prevention and/or treatment of retinal diseases such as atrophic AMD.

Glycyrrhizin protects against sodium iodate-induced RPE and retinal injury though activation of AKT and Nrf2/HO-1 pathway.

Glycyrrhizin is a bioactive triterpenoid saponin extracted from a traditional Chinese medicinal herb, glycyrrhiza, and has been reported to protect the organs such as liver and heart from injuries. However, there is no report about the effects of glycyrrhizin on atrophic age‐related macular degeneration (AMD). This study investigated the effects of glycyrrhizin on retinal pigment epithelium (RPE) in vitro and retina of mice in vivo treated with sodium iodate (SI). Glycyrrhizin significantly inhibited SI‐induced reactive oxygen species (ROS), and decreased apoptosis of RPE in vitro. The underlying mechanisms included increased phosphorylation of Akt, and increased expression of nuclear factor erythroid 2‐related factor2 (Nrf‐2) and HO‐1, thereby protecting RPE from SI‐induced ROS and apoptosis. Furthermore, glycyrrhizin significantly decreased the apoptosis of retinal cells in vivo, resulting in the inhibition of thinning of retina, decreasing the number of drusen and improving the function of retina. These findings suggested that glycyrrhizin may be a potential candidate for the treatment of atrophic AMD in clinical practice.

Efficacy of novel selective NLRP3 inhibitors in human and murine retinal pigment epithelial cells.

NLRP3 inflammasome activation in the retinal pigment epithelium (RPE) is observed in atrophic age-related macular degeneration (AMD), and pharmacological NLRP3 inhibition may provide a therapeutic strategy to halt disease progression. We tested selective NLRP3 inhibitors (IFM-514, IFM-632, and CRID3) for their efficacy in human and murine RPE cells. Inflammasome activation was induced in primary human RPE cells and ARPE-19 cells following priming with IL-1α by different stimuli, including lysosomal membrane permeabilization by leucyl-leucine methyl ester (Leu-Leu-OMe), oxidative damage induced by hydrogen peroxide, lipofuscin-mediated photooxidative damage induced by incubation with 4-hydroxynonenal-modified photoreceptor outer segments and subsequent blue light irradiation, and P2X7 receptor activation by benzoylbenzoyl-ATP. Independent of the applied activation mechanism, treatment with the NLRP3 inhibitors IFM-632, IFM-514, and CRID3 resulted in a significant suppression of inflammasome activation as assessed by IL-1β and LDH release. Likewise, inflammasome activation in blue light-irradiated Abca4-/- mouse and Leu-Leu-OMe-treated wild-type mouse RPE/choroid/sclera eye cups was significantly reduced by treatment with the NLRP3 inhibitors. These results indicate that the investigated selective NLRP3 inhibitors are effective in human and murine RPE cells, thus representing promising agents for the future evaluation of inflammasome inhibition as a therapeutic strategy in atrophic AMD. KEY MESSAGES: • NLRP3 inhibitors suppress inflammasome activation in human RPE cells independent of trigger. • Light-induced inflammasome activation in Abca4-/- mouse eye cups is reduced by NLRP3 inhibitors. • Novel selective NLRP3 inhibitors are effective in human and murine RPE cells. • Promising compounds for pharmaceutical intervention in atrophic AMD.

Progress in the treatment of atrophic age-related macular degeneration

Atrophic age-related macular degeneration (AMD) does not show obvious loss of visual function in the early stage, so it is not easy to be taken seriously. In the advanced stage, most of the patients suffered from macular area retinal map atrophy, which affected night vision and central vision. Drugs currently used in clinical or clinical trials to treat atrophic AMD include drugs for improving choroidal perfusion, reducing the accumulation of harmful substances, preventing oxidative stress injury, inhibiting inflammatory reactions, as well as neuroprotectants and lipid metabolism drugs. Stem cell transplantation for atrophic AMD is currently the most promising treatment. In theory, it is feasible to replace atrophic AMD with retinal photoreceptor cells and RPE cells derived from human stem cell differentiation. However, there are still many problems to be solved, such as how to improve the efficiency of directional differentiation of seed cells and how to ensure the safe and effective RPE cell transplantation and survival after transplantation. At present, several studies have found that multiple locus mutations are associated with atrophic AMD, so gene therapy also plays an important role in the development of the disease. Key words: Macular degeneration/therapy; Geographic atrophy; Review

Intravitreal use of bone marrow mononuclear fraction containing CD34+ stem cells in patients with atrophic age-related macular degeneration.

PurposeTo evaluate the therapeutic potential and safety of intravitreal injections of bone marrow mononuclear fraction (BMMF) containing CD34+ cells in patients with atrophic age-related macular degeneration (AMD).MethodsTen patients with atrophic AMD and best-corrected visual acuity (BCVA) in the worse-seeing eye of ≤20/100 were enrolled in this study. The bone marrow from all patients was aspirated and processed for mononuclear cell separation. A 0.1 mL suspension of BMMF CD34+ cells was injected into the vitreous cavity of the worse-seeing eye. Patients were evaluated at Baseline and 1,3,6,9 and 12 months after injection. Ophthalmic evaluation included BCVA measurement, microperimetry, infrared imaging, fundus autofluorescence and SD-optical coherence tomography at all study visits. Fluorescein angiography was performed at Baseline and at 6 and 12 months after intravitreal therapy.ResultsAll patients completed the 6-month follow-up, and six completed the 12-month follow-up. Prior to the injection, mean BCVA was 1.18 logMAR (20/320−1), ranging from 20/125 to 20/640−2, and improved significantly at every follow-up visit, including the 12-month one, when BCVA was 1.0 logMAR (20/200) (P<0.05). Mean sensitivity threshold also improved significantly at 6, 9 and 12 months after treatment (P<0.05). Considering the area of atrophy identified by fundus autofluorescence, significant mean BCVA and mean sensitivity threshold improvement were observed in patients with the smallest areas of atrophy. Fluorescein angiography did not identify choroidal new vessels or tumor growth.ConclusionThe use of intravitreal BMMF injections in patients with AMD is safe and is associated with significant improvement in BCVA and macular sensitivity threshold. Patients with small areas of atrophy have a better response. The paracrine effect of CD34+ cells may explain the functional improvement observed; however, larger series of patients are necessary to confirm these preliminary findings.

Intravitreal therapies for non-neovascular age-related macular degeneration with intraretinal or subretinal fluid

Abstract Objective To evaluate the efficacy of intravitreal therapies in cases of atrophic age-related macular degeneration (AMD) with subretinal or intraretinal fluid. Methods A retrospective review was made of the clinical charts of patients diagnosed with atrophic AMD with subretinal or intraretinal fluid. Fundus photographs and spectral-domain optical coherence tomography images were examined, and an analysis was made on the presence of fluid and its density. Neovascularisation was ruled out by fluorescein and/or indocyanine green angiography. Results The study included 14 eyes from 13 patients with a mean age of 72.64 years and a mean follow-up of 80.5 weeks. Intraretinal fluid was observed in 6 eyes (42.9%), while subretinal fluid was shown in 8 eyes (57.1%), with high density in 4 eyes (28.5%), and low density in 4 eyes (28.5%). Snellen best-corrected visual acuity improved from 0.37 at baseline to 0.56 at the final visit (P = 0.002). Central subfield thickness (microns) significantly decreased (P Conclusions Cases of atrophic AMD may present with subretinal or intraretinal fluid in the absence Neovascularisation. Further studies are required to analyze the value of this finding as a risk factor of developing advanced forms of AMD, as well as the efficacy of intravitreal therapies.

Terapias intravítreas en degeneración macular asociada a la edad no neovascular con fluido intrarretiniano o subretiniano

ObjectiveTo evaluate the efficacy of intravitreal therapies in cases of atrophic age-related macular degeneration (AMD) with subretinal or intraretinal fluid. MethodsA retrospective review was made of the clinical charts of patients diagnosed with atrophic AMD with subretinal or intraretinal fluid. Fundus photographs and spectral-domain optical coherence tomography images were examined, and an analysis was made on the presence of fluid and its density. Neovascularisation was ruled out by fluorescein and/or indocyanine green angiography. ResultsThe study included 14 eyes from 13 patients with a mean age of 72.64 years and a mean follow-up of 80.5 weeks. Intraretinal fluid was observed in 6 eyes (42.9%), while subretinal fluid was shown in 8 eyes (57.1%), with high density in 4 eyes (28.5%), and low density in 4 eyes (28.5%). Snellen best-corrected visual acuity improved from 0.37 at baseline to 0.56 at the final visit (P=.002). Central subfield thickness (microns) significantly decreased (P<.001) from 291.0 at baseline to 228.9 at the final visit. Eight eyes received ranibizumab, 5eyes received bevacizumab, and one case received triamcinolone. ConclusionsCases of atrophic AMD may present with subretinal or intraretinal fluid in the absence Neovascularisation. Further studies are required to analyse the value of this finding as a risk factor of developing advanced forms of AMD, as well as the efficacy of intravitreal therapies.

Genome-wide analysis of single nucleotide polymorphisms in patients with atrophic age-related macular degeneration in oldest old Han Chinese.

The aim of this study was to identify disease-associated loci in oldest old Han Chinese with atrophic age-related macular degeneration (AMD). This genome-wide association study (GWAS) only included oldest old (≥95 years old) subjects in Rugao County, China. Thirty atrophic AMD patients and 47 age-matched non-AMD controls were enrolled. The study subjects underwent a complete ophthalmic examination. Genomic DNA was extracted from peripheral blood samples. Single nucleotide polymorphisms (SNPs) were scanned by Genome-Wide Human Mapping SNP 6.0 Arrays and GeneChip Scanner 3000 7G. The results were read and analyzed by the Affymetrix Genotyping Console software. We filtered out the SNPs with a no-call rate ≥10%, MAF P < 0.05, and HWE P < 0.001. The remaining 561,277 SNPs were included in the association analysis. We found that the following 2 SNPs had the highest association with atrophic AMD: rs7624556 (located on 3q24) and rs13119914 (located on 4q34.3). In conclusion, we identified two atrophic AMD-associated SNPs (rs7624556 and rs13119914) in an oldest old Han Chinese population. This finding may lead to new strategies for screening of atrophic AMD for Han Chinese.

Characteristics of spectral-domain optical coherence tomography of drusen in atrophic age-related macular degeneration

Objective To observe the morphologic characteristics of drusen in atrophic age-related macular degeneration (AMD) by spectral domain optical coherence tomography (SD-OCT).Methods Fifty-four patients (84 eyes) with macular drusen and atrophic AMD,and 56 age-matched control patients (56 eyes) with cataract were included in this study.Atrophic AMD patients were divided into two groups:D1 group with drusen involving the fovea (42 eyes) and D2 group with drusen not involving the fovea (42 eyes).The SD-OCT images in macular (6 mm× 6 mm scans) were acquired,and the foveal retinal thickness (FRT) was measured.The size,morphology,inner reflection,homogeneity of drusen and its relationship with surrounding tissues were analyzed.Results The FRT of D1 group,D2 group and control group were (160.90±38.47),(194.21±26.11),(222.42± 19.29) μm respectively.The FRT of D1 group and D2 group were thinner than that of control group (F=57.08,P=0.00).Totally 1124 drusen were found by SD-OCT images in 84 eyes,with an average of 10.84 drusen in each eye.3.0％,12.5％ and 84.5％ of all 1124 drusen were small,medium and large sized respectively.56.6％,14.2％,20.4％ and 8.8％ of all drusen were dome,pointed,saw-toothed and basal-shaped respectively.17.1 ％,57.5％ and 25.4％ of all drusen had low,medium and high internal reflectivity respectively.The internal reflectivity of 65.6％,2.8％ and 31.7％ of all drusen were homogeneous,nonhomogeneous with core,and nonhomogeneous without core respectively.Overlying retinal pigment epithelium (RPE) damage and photoreceptor inner segment/outer segment (IS/OS) junction damage were presented in 34.5 ％ and 24.8 ％ drusen respectively.The most common type of drusen was dome-shape,homogeneous,with medium internal reflectivity,and without overlying RPE or IS/OS junction damage (81.0％).Conclusions The FRT becomes thinner in patients with drusen.The most common drusen types are dome-shaped,homogeneous,with medium internal reflectivity,and without overlying RPE or IS/OS junction damage. Key words: Retinal drusen/diagnosis; Tomography, optical coherence; Macular degeneration/ diagnosis; Diagnostic imaging

CCR2+ monocytes infiltrate atrophic lesions in age‐related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice

Atrophic age-related macular degeneration (AMD) is associated with the subretinal accumulation of mononuclear phagocytes (MPs). Their role in promoting or inhibiting retinal degeneration is unknown. We here show that atrophic AMD is associated with increased intraocular CCL2 levels and subretinal CCR2+ inflammatory monocyte infiltration in patients. Using age- and light-induced subretinal inflammation and photoreceptor degeneration in Cx3cr1 knockout mice, we show that subretinal Cx3cr1 deficient MPs overexpress CCL2 and that both the genetic deletion of CCL2 or CCR2 and the pharmacological inhibition of CCR2 prevent inflammatory monocyte recruitment, MP accumulation and photoreceptor degeneration in vivo. Our study shows that contrary to CCR2 and CCL2, CX3CR1 is constitutively expressed in the retina where it represses the expression of CCL2 and the recruitment of neurotoxic inflammatory CCR2+ monocytes. CCL2/CCR2 inhibition might represent a powerful tool for controlling inflammation and neurodegeneration in AMD.

Custom‐devised and generic digital enhancement of images for people with maculopathy

The purpose of this study was to compare the effectivity, in terms of the potential usefulness, of digital filters based on either contrast sensitivity (CS) or supra-threshold contrast matching (CM) in enhancing pictures images for people with maculopathy and to investigate whether generic filters (not based on an individual's vision loss) are equally as effective. Effectivity is measured by changes in perceived visibility. Thirty-five subjects with maculopathy, aged 20-92 years, took part [13 atrophic age-related macular degeneration (ARMD), 14 exudative ARMD, and 8 juvenile macular dystrophy (JMD)]. CS and supra-threshold CM were measured. A range of CS filters (1 or 2-octave wide band-pass filter using a Gabor or polynomial envelope) with different strengths were developed based on the ratio of the individual's contrast threshold and that of a normal age-related group. Similarly filters were developed based on CM at 3.6% and 27.9% contrast. The following generic filters were also applied with different 'strengths': edge enhancement; sharpening; contrast enhancement; Peli's adaptive enhancement; difference of Gaussian; and an equi-emphasis band-pass filter. The filters were applied to images of faces and general scenes. Subjects were asked to rank the perceived visibility of images (to obtain the best version of each filter) and then to rate the perceived visibility of each image filtered with a particular filter. In general, subjects with atrophic ARMD and JMD preferred the weaker versions of most of the filters, while those with exudative ARMD did not show such a clear preference. Generally, images of faces were preferred with less enhancement than scenes. The filters based on CM were rated as giving significant improvement, while those based on CS and peak emphasis were not preferred. Of the generic filters, the Peli adaptive enhancement filter was most frequently rated as giving a significant improvement (p < 0.05) followed by the contrast enhancement filter. They gave the same perceived enhancement as the custom-devised filters. Generic filters, which are easier to apply than the custom-devised filters, are appropriate for rehabilitation purposes.

The Coexistence of Age-Related Macular Degeneration and Retinitis Pigmentosa in Three Unrelated Families

Purpose: To describe the clinical, electroretinographic (ERG) and genetic findings in three unrelated families with a coexistence of severe, atrophic age-related macular degeneration (ARMD) in the first generation and rod-cone retinitis pigmentosa (RP) in the second generation. Methods: Patients underwent complete ophthalmologic examination, fluorescein angiography (FA), Humphrey visual field (HVF) and ERG analyses. Genetic screening was conducted to search for mutations of the ABCA4, peripherin/RDS, and GCAP-1 genes. Results: In each of the three families, the mother demonstrated severe vision loss from geographic atrophy (GA). At least one child in each family demonstrated clinical and ERG evidence of rod-cone RP with a flat or severely depressed scotopic response and a variably depressed photopic response. Genetic screening was negative for known mutations in ABCA4, peripherin/RDS and GCAP-1 genes. Conclusions: The coexistence of ARMD and RP in different members of one family lacks precedent in the literature. Here we present three families with severe, atrophic ARMD (GA) in the mothers and rod-cone RP in the children, which may represent a novel phenotype. A currently unidentified genetic mutation with variable expression and/or gene manifesting a carrier state may explain the presence of these two diseases in the same family.

Progression of Geographic Atrophy and Impact of Fundus Autofluorescence Patterns in Age-related Macular Degeneration

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). Prospective longitudinal multicenter natural history study. 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). 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). 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.