Reticular Pseudodrusen Research Articles

Differentiating drusen: Drusen and drusen-like appearances associated with ageing, age-related macular degeneration, inherited eye disease and other pathological processes.

Drusen are discussed frequently in the context of their association with age-related macular degeneration (AMD). Some types may, however, be regarded as a normal consequence of ageing; others may be observed in young age groups. They also occur in a number of inherited disorders and some systemic conditions. Whilst drusen are classically located external (sclerad) to the retinal pigment epithelium, accumulations of material internal (vitread to) this layer can display a drusen-like appearance, having been variously termed pseudodrusen or subretinal drusenoid deposits. This review first briefly presents an overview of drusen biogenesis and subclinical deposit. The (frequently overlapping) subtypes of clinically detectable deposit, seen usually in the context of ageing or AMD, are then described in more detail, together with appearance on imaging modalities: these include hard and soft drusen, cuticular drusen, reticular pseudodrusen and "ghost drusen". Eye disorders other than AMD which may exhibit drusen or drusen-like features are subsequently discussed: these include monogenic conditions as well as conditions with undefined inheritance, the latter including some types of early onset drusen such as large colloid drusen. A number of systemic conditions in which drusen-like deposits may be seen are also considered. Throughout this review, high resolution images are presented for most of the conditions discussed, particularly the rarer ones, providing a useful reference library for images of the range of conditions associated with drusen-like appearances. In the final section, some common themes are highlighted, as well as a brief discussion of some future avenues for research.

Infrared reflectance imaging in age-related macular degeneration.

PurposeThe purpose of this article is to describe the appearance of age‐related macular degeneration (AMD) phenotypes using infrared (IR) reflectance imaging. IR reflectance imaging of the retina has the potential to highlight specific sub‐retinal features and pathology. However, its role in macular disease, specifically AMD, is often underestimated and requires clarification.Recent findingsRecent advances in clinical methods, imaging and scientific knowledge may be integrated to improve the accuracy of disease stratification in AMD. In particular, IR imaging holds an underutilised sensitivity to detect reticular pseudodrusen, which have been repeatedly described as a high‐risk sign for late AMD.SummaryThis article provides clinically relevant descriptions of AMD phenotypes using IR reflectance imaging. The findings are integrated with images from cases seen at the Centre for Eye Health. As primary eye‐care providers assume a critical role in the detection, diagnosis and management of AMD, we also provide a chair‐side reference to assist clinicians in interpreting IR images in AMD.

Prevalence of reticular pseudodrusen in newly presenting adult onset foveomacular vitelliform dystrophy.

PurposeTo report the association and prevalence of reticular pseudodrusen (RPD) in eyes with newly presenting adult onset foveomacular vitelliform dystrophy (AFVD). To compare the strength of association with other pathologies resulting from dysfunction of the choroid-Bruch's membrane-retinal pigment epithelium (RPE) complex, including eyes with geographic atrophy (GA) and angioid streaks.MethodsRetrospective single-centre review of all consecutive newly presenting AFVD. Multimodal imaging with spectral domain optical coherence tomography, fundus photographs, red-free/blue light images, and fundus fluorescein angiograms were graded for the presence of RPD. For comparison, all consecutive newly presenting cases of GA and eyes with angioid streaks were studied.ResultsFifteen (15) patients were identified with AFVD (mean age of 77.3 years; 73.3% female). Mean age of patients with AFVD and RPD was 80.5 years (SD 3.7), whereas that of patients with AFVD without RPD was 75.1 years (SD 7.0). This age difference did not reach statistical significance, P=0.1. Six (40%) had identifiable RPD; being a bilateral finding in 100% of patients. No males with AFVD and RPD were identified. A total of 92 eyes presented with GA. Twenty-three (23) of these (25.0%) had RPD. Twelve (12) patients presented with identifiable angioid streaks, with 4 (36.4%) having RPD.ConclusionRPD are a frequent finding in eyes with newly presenting AFVD; not being restricted to AMD, but a finding common among diseases where pathophysiological mechanisms involve damage to Bruch's membrane and the RPE, whether genetic or degenerative. Our study supports the concept that they occur with high but variable frequencies in eyes with various pathologies.

Accuracy of fundus autofluorescence imaging for the diagnosis and monitoring of retinal conditions: a systematic review.

Natural fluorescence in the eye may be increased or decreased by diseases that affect the retina. Imaging methods based on confocal scanning laser ophthalmoscopy (cSLO) can detect this 'fundus autofluorescence' (FAF) by illuminating the retina using a specific light 'excitation wavelength'. FAF imaging could assist the diagnosis or monitoring of retinal conditions. However, the accuracy of the method for diagnosis or monitoring is unclear. To conduct a systematic review to determine the accuracy of FAF imaging using cSLO for the diagnosis or monitoring of retinal conditions, including monitoring of response to therapy. Electronic bibliographic databases; scrutiny of reference lists of included studies and relevant systematic reviews; and searches of internet pages of relevant organisations, meetings and trial registries. Databases included MEDLINE, EMBASE, The Cochrane Library, Web of Science and the Medion database of diagnostic accuracy studies. Searches covered 1990 to November 2014 and were limited to the English language. References were screened for relevance using prespecified inclusion criteria to capture a broad range of retinal conditions. Two reviewers assessed titles and abstracts independently. Full-text versions of relevant records were retrieved and screened by one reviewer and checked by a second. Data were extracted and critically appraised using the Quality Assessment of Diagnostic Accuracy Studies criteria (QUADAS) for assessing risk of bias in test accuracy studies by one reviewer and checked by a second. At all stages any reviewer disagreement was resolved through discussion or arbitration by a third reviewer. Eight primary research studies have investigated the diagnostic accuracy of FAF imaging in retinal conditions: choroidal neovascularisation (one study), reticular pseudodrusen (three studies), cystoid macular oedema (two studies) and diabetic macular oedema (two studies). Sensitivity of FAF imaging using an excitation wavelength of 488 nm was generally high (range 81-100%), but was lower (55% and 32%) in two studies using longer excitation wavelengths (514 nm and 790 nm, respectively). Specificity ranged from 34% to 100%. However, owing to limitations of the data, none of the studies provide conclusive evidence of the diagnostic accuracy of FAF imaging. No studies on the accuracy of FAF imaging for monitoring the progression of retinal conditions or response to therapy were identified. Owing to study heterogeneity, pooling of diagnostic outcomes in meta-analysis was not conducted. All included studies had high risk of bias. In most studies the patient spectrum was not reflective of those who would present in clinical practice and no studies adequately reported how FAF images were interpreted. Although already in use in clinical practice, it is unclear whether or not FAF imaging is accurate, and whether or not it is applied and interpreted consistently for the diagnosis and/or monitoring of retinal conditions. Well-designed prospective primary research studies, which conform to the paradigm of diagnostic test accuracy assessment, are required to investigate the accuracy of FAF imaging in diagnosis and monitoring of inherited retinal dystrophies, early age-related macular degeneration, geographic atrophy and central serous chorioretinopathy. This study is registered as PROSPERO CRD42014014997. The National Institute for Health Research Health Technology Assessment programme.

Correlation of Histologic Features with In Vivo Imaging of Reticular Pseudodrusen

To determine the histologic and cellular correlates in the retina and retinal pigment epithelium (RPE) with the presence of optical coherence tomography-defined reticular pseudodrusen (RPD). Observation case using immunocytochemistry of an exenterated eye with immediate fixation after removal. Two patients, one with confirmed RPD and the other with mid-peripheral drusen, underwent multimethod imaging before exenteration and immediate fixation of the posterior eyecup for high-resolution immunocytochemical analysis. Optical coherence tomography (OCT) was compared with high-resolution immunocytochemistry using a range of cellular markers to determine changes in the RPE, photoreceptors, and gliosis. Correlations of the appearance of reticular pseudodrusen on OCT and immunocytochemical analysis. Reticular pseudodrusen were deposits juxtaposed to photoreceptor outer segments extending through the outer nuclear layer and even beyond the outer limiting membrane. Deposits were rich invitronectin, photoreceptor-associated proteins, and Iba1-immunoreactive immune cells. In contrast to conventional drusen the lipid stain Oil Red O failed to stain RPD. Cellular analysis revealed that RPD were associated with photoreceptor disruption and loss and localized gliosis. In addition, anomalies in the RPE were observed. Reticular pseudodrusen represent subretinal deposits that extend through the outer nuclear layer, affect photoreceptor integrity, and are associated with retinal gliosis and RPE damage.

Reticular Pseudodrusen in Intermediate Age-Related Macular Degeneration: Prevalence, Detection, Clinical, Environmental, and Genetic Associations.

To determine the prevalence of reticular pseudodrusen (RPD) and their detection using multimodal imaging in patients with bilateral large drusen, and examine their clinical, demographic, environmental, and genetic associations. Three hundred participants with bilateral large drusen (>125 μm) underwent color fundus photography (CFP), near-infrared reflectance (NIR), fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (SD-OCT) imaging. Demographic information, smoking, and medical history were recorded, and a blood sample was obtained and genotyped to identify the risk alleles of the CFH and ARMS2 genes. Reticular pseudodrusen were detected in 28.2% eyes of 29.0% participants using NIR and SD-OCT combined, but CFP and FAF detected only 42% and 89%, respectively, of these eyes with RPD. Participants with RPD were significantly older than those without (P < 0.001), but there was no significant difference in sex distribution, smoking history, cardiovascular factors, and minor allele frequency of the CFH gene (P > 0.173). However, the minor allele frequency of the ARMS2 gene was significantly higher in participants with RPD (P = 0.002). The presence of RPD was also independently associated with the presence of atrophic changes (including nascent geographic atrophy and drusen-associated atrophy detected on SD-OCT; P = 0.043). Reticular pseudodrusen were detected on NIR and SD-OCT in more than a quarter of participants with bilateral large drusen, being often overlooked with CFP. Those with RPD had a higher frequency of the ARMS2 risk variant, and eyes with RPD were more likely to have atrophic changes. These findings are important to consider when managing patients with intermediate AMD.

TYPE 2 (SUBRETINAL) NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH PURE RETICULAR PSEUDODRUSEN PHENOTYPE.

To report the association of pure type 2 neovascularization (NV) in age-related macular degeneration occurring almost exclusively in patients with reticular pseudodrusen. An observational retrospective cohort study of all eyes receiving antivascular endothelial growth factor therapy for newly diagnosed neovascular age-related macular degeneration by a single practitioner over a 6-year period. Only patients with treatment-naive, pure type 2 NV who also had either pre-neovascular imaging of the study eye or imaging of a nonneovascular fellow eye available to determine baseline characteristics including drusen type and choroidal thickness were incuded. Of 694 patients treated for neovascular age-related macular degeneration, only 8 met the inclusion criteria with pure type 2 NV. Of these, 7 (88%) had exclusively reticular pseudodrusen (5 in the nonneovascular fellow eye, 2 in the study eye before developing NV). Six (75%) patients in the affected neovascular eye and 6 (75%) in the fellow nonneovascular eye had choroidal thickness <120 μm. Mean follow-up was 46 months (range, 3.0-63.3). Best-corrected vision improved from 20/89 (range, 20/30-20/796) at baseline to 20/60 (range, 20/20-20/399) at last follow-up. Pure type 2 NV is rare in age-related macular degeneration, occurring almost exclusively in patients with reticular pseudodrusen and thin choroids.

Rare Genetic Variants Associated With Development of Age-Related Macular Degeneration.

Rare variants in the complement genes CFH, CFI, C9, and C3 have been found to be highly associated with age-related macular degeneration (AMD); however, the effect on clinical characteristics and familial segregation by these variants is lacking. To determine the contribution of rare CFH Arg1210Cys, CFI Gly119Arg, C9 Pro167Ser, and C3 Lys155Gln variants in the development of AMD in 22 multiplex families and to describe clinical differences in carriers vs noncarriers in these families and a large case-control cohort. This retrospective case-control study included 114 affected and 60 unaffected members of 22 multiplex families with AMD as well as 1589 unrelated patients with AMD and 1386 unrelated control individuals enrolled in the European Genetic Database (EUGENDA). Patients were recruited from March 29, 2006, to April 26, 2013, and data were collected from April 20, 2012, to May 7, 2014. All participants underwent an extensive ophthalmic examination and completed a questionnaire. Venous blood samples were obtained from all participants for genetic analysis, including whole-exome sequencing and measurements of complement activation. Data were analyzed from September 23, 2014, to November 4, 2015. Differences between carriers and noncarriers of rare variants in age at onset of symptoms, the family history of AMD, complement activation levels (C3d:C3 ratio), the presence of reticular pseudodrusen, and AMD phenotype. Among the 114 affected and 60 unaffected members of 22 multiplex families with AMD and the 1598 unrelated patients with AMD and 1386 controls in the EUGENDA cohort who underwent analysis, the presence of the CFI Gly119Arg, C9 Pro167Ser, or C3 Lys155Gln variant was confirmed in 18 individuals in 5 families but did not completely segregate with the disease. In the case-control cohort, the 91 affected carriers of these variants were younger at symptom onset (mean [SD] age, 67.4 [8.5] vs 71.3 [8.9] years; P = .01) and more often reported a positive family history (35 of 79 [44.3%] vs 367 of 1201 [30.6%]; P = .008) compared with the 1498 noncarriers. Patients with advanced atrophic AMD carried these rare variants more frequently than patients with neovascular AMD (11 of 93 [11.8%] vs 40 of 835 [4.8%]; P = .04). Previously reported rare variants do not completely segregate within families with AMD. However, patients carrying these rare variants differ clinically from noncarriers by an earlier age at symptom onset, higher prevalence of a positive family history, and AMD phenotype. These results suggest that genetic tests for AMD might be designed to detect common and rare genetic variants, especially in families, because rare variants contribute to the age at onset and progression of the disease.

Prevalence and Genetic Characteristics of Geographic Atrophy among Elderly Japanese with Age-Related Macular Degeneration.

ObjectiveTo investigate the prevalence and genetic characteristics of geographic atrophy (GA) among elderly Japanese with advanced age-related macular degeneration (AMD) in a clinic-based study.MethodsTwo-hundred and ninety consecutive patients with advanced AMD were classified into typical neovascular AMD, polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP) or geographic atrophy (GA). Genetic variants of ARMS2 A69S (rs10490924) and CFH I62V (rs800292) were genotyped using TaqMan Genotyping Assays. The clinical and genetic characteristics were compared between patients with and without GA.ResultsThe number of patients diagnosed as having typical neovascular AMD, PCV, RAP and GA were 98 (33.8%), 151 (52.1%), 22 (7.5%) and 19 (6.6%), respectively. Of 19 patients with GA, 13 patients (68.4%) had unilateral GA with exudative AMD in the contralateral eye. Patients with GA were significantly older, with a higher prevalence of reticular pseudodrusen, bilateral involvement of advanced AMD and T-allele frequency of ARMS2 A69S compared with those with typical AMD and PCV; although there were no differences in the genetic and clinical characteristics among patients with GA and RAP.ConclusionsThe prevalence of GA was 6.6% among elderly Japanese with AMD. Patients with GA and RAP exhibited genetic and clinical similarities.

PREVALENCE OF RETICULAR PSEUDODRUSEN IN AGE-RELATED MACULAR DEGENERATION USING MULTIMODAL IMAGING.

To determine the rate of reticular pseudodrusen (RPD) in age-related macular degeneration using multimodal imaging, including color fundus photography, the blue channel image of fundus photography, infrared reflectance, fundus autofluorescence, multicolor imaging, and spectral domain optical coherence tomography, as well as to compare the sensitivities and specificities of these modalities for detecting RPD. This prospective study included 243 eyes from 125 consecutive patients with age-related macular degeneration. They underwent fundus examination including color fundus photography, blue channel, infrared reflectance, fundus autofluorescence, multicolor imaging, and spectral domain optical coherence tomography in both eyes. To be considered as having RPD, eyes had to have reticular patterns on spectral domain optical coherence tomography in a large studied cube of 30° × 25° or on infrared reflectance with at least one other examination. The mean age of the 125 patients was 81.1 years (± 8.1). Eighty-six patients (68.8%) were diagnosed with RPD. Spectral domain optical coherence tomography, infrared reflectance, and multicolor imaging had the highest sensitivity (99.3, 84.6, and 87.1%, respectively) and specificity (100%). The color fundus photography, blue channel, and fundus autofluorescence had lower sensitivity to detect RPD. Reticular pseudodrusen is frequently associated with soft drusen in patients with age-related macular degeneration. As RPD may be rarely located only in the perifoveal area, spectral domain optical coherence tomography with a larger cube (30 × 25°) than that usually used (20 × 20°) had the highest sensitivity and specificity to detect RPD and is recommended to optimize the rate of detection.

Macular drusen variability: multimodal imaging potential

The purpose of the study – to assess clinical feature of MD using modern digital imaging technologies. Patients with both hard and soft drusen were studied using fluorescein angiography, swept-source optical coherence tomography (OCT), OCT-angiography, autofluorescence (both short-wavelength and near infra-red), scanning laser ophthalmoscopy in Multicolor mode. The retina, choroid and vitreoretinal interface were assessed on 50 patients with AMD and drusen using different imaging modalities. An additional group of the study was presented by 5 patients with geographic atrophy (GA) formed as a result of soft drusen fading, where retrospective assessment of the OCT scans was performed with special attention to the signs of soft drusen regression associated with atrophy of the overlying RPE. Two types of hard drusen were defined as the reticular pseudodrusen and the cuticular drusen. The qualitative and comparative analysis of data for each type of MD was performed. Vitreoretinal interface evaluation demonstrated the correlation between vitreomacular adhesion and mixed reticular and cuticular drusen. The choroidal thickness assessment in 9 different macular sectors in drusenoid eyes does not reveal a significant difference with control group. All of the analysed drusen-faded-eyes initially had been presented with OCT patterns of “nascent” GA. The modern retinal imaging techniques enable new approach to the diagnostic differentiation and description of various macular drusen types. The value of these methods for AMD prognosis is yet to be further investigated.

Predictive Value of Outer Retina En Face OCT Imaging for Geographic Atrophy Progression.

We determined if the ellipsoid zone (EZ) disruption pattern could be predictive of the geographic atrophy (GA) pattern at 1 year in dry age-related macular degeneration (AMD). A retrospective study was done of dry eyes in patients with AMD and GA from July to November 2013. Eyes with previous choroidal neovascularization were excluded. Based on spectral domain optical coherence tomography (SD-OCT), the GA was assessed at each timepoint, using a sub-RPE slab derived from the Cirrus Advanced RPE Analysis software encompassing the RPE (sub-RPE slab). Disruption of the EZ also was assessed at baseline, using en face extraction of a 20-μm-thick slab, 20 μm above the RPE (EZ slab) encompassing the EZ band using two different algorithms (RPE and RPE-fit). The EZ disruption area surrounding GA at baseline was quantified using ImageJ software. Primary endpoint was to identify en face pattern similarities between the baseline EZ disruption and the 1-year GA. Secondary endpoint was to correlate the baseline EZ disruption area surrounding GA with the GA enlargement over 1 year. Statistical analysis was performed using a correlation test (Pearson) and a t-test. We included 37 eyes of 31 patients with dry AMD. En face EZ disruption pattern correlated in two-thirds of cases with the 1-year GA pattern using both algorithms. The EZ disruption area surrounding GA at baseline and GA enlargement over 1 year were poorly correlated when RPE-fit algorithm (R = 0.17) was used. The correlation was still poor using an RPE algorithm (R = 0.38), but increased after selection of eyes without reticular pseudodrusen (R = 0.79). The EZ disruption pattern could be an indicator for GA pattern progression, but is not a good quantitative tool to predict the size of GA in the overall population over a 1-year period except for patients without reticular pseudodrusen. The results in this specific population must be confirmed by further studies.

Reticular Pseudodrusen and Their Association with Age-Related Macular Degeneration: The Melbourne Collaborative Cohort Study

To determine the prevalence of reticular pseudodrusen (RPD) and its association with age-related macular degeneration (AMD) and AMD risk factors in a large sample. Community-based cohort study in Melbourne, Victoria, Australia. A total of 21,130 participants 48 to 86 years of age available for ophthalmic assessment at follow-up from 2003 through 2007. Lifestyle, diet, and anthropometric measurements were obtained at baseline and follow-up. At follow-up, digital macular color photographs were graded for early, intermediate, and late AMD as well as the presence of RPD. Data were analyzed using multinomial logistic regression controlling for age, gender, smoking, country of birth, and diet. Detection of RPD based on color fundus photographs. Prevalence of RPD was 0.41% (87 of 21,130 participants), with 51% having bilateral RPD. Patients with RPD were older compared with patients with large drusen (>125 μm; 76±4 vs. 68±9 years; P < 0.001). Increasing age, female gender, being a current smoker, as well as focal pigmentary abnormalities and large drusen (>125 μm) were associated with a higher prevalence of RPD. Presence of geographic atrophy (GA) was associated with the highest odds of having RPD (odds ratio [OR], 153; 95% confidence interval [CI], 53-442), followed by choroidal neovascularization (CNV; OR, 90; 95% CI, 26-310), intermediate AMD (OR, 33; 95% CI, 14-77), and early AMD (OR, 12; 95% CI, 5-31) compared with those with no AMD. The ARMS2 single nucleotide polymorphism (SNP) rs10490924, HTRA1 SNPs rs11200638 and rs3793917, and CFH SNPs rs393955, rs1061170, and rs2274700 were associated with increased prevalence of RPD (all P < 0.05). Reticular pseudodrusen are highly concurrent with AMD and have similar associations with known AMD risk factors such as age, gender, smoking, and genetic risk factors. Reticular pseudodrusen are associated more strongly with GA than with CNV. Although RPD are not specific to AMD, they are likely to be a strong risk factor for progression to late-stage AMD, similar to focal pigmentary abnormalities and large drusen.

The Relationship Between Reticular Pseudodrusen and Severity of AMD

The Relationship Between Reticular Pseudodrusen and Severity of AMD

RETICULAR PSEUDODRUSEN ON INFRARED IMAGING ARE TOPOGRAPHICALLY DISTINCT FROM SUBRETINAL DRUSENOID DEPOSITS ON EN FACE OPTICAL COHERENCE TOMOGRAPHY.

To evaluate the quantitative and topographic relationship between reticular pseudodrusen (RPD) on infrared reflectance (IR) and subretinal drusenoid deposits (SDD) on en face volumetric spectral domain optical coherence tomography. Reticular pseudodrusen were marked on IR images by a masked observer. Subretinal drusenoid deposits were visualized on en face sections of spectral domain optical coherence tomography below the external limiting membrane and identified by a semiautomated technique. Control RPD lesions were generated in a random distribution for each IR image. Binary maps of control and experimental RPD and SDD were merged and analyzed in terms of topographic localization and quantitative drusen load comparison. A total of 54 eyes of 41 patients diagnosed with RPD were included in this study. The average number of RPD lesions on IR images was 320 ± 44.62 compared with 127 ± 26.02 SDD lesions on en face (P < 0.001). The majority of RPD lesions did not overlap with SDD lesions and were located >30 μm away (92%). The percentage of total SDD lesions overlapping RPD was 2.91 ± 0.87% compared with 1.73 ± 0.68% overlapping control RPD lesions (P < 0.05). The percentage of total SDD lesions between 1 and 3 pixels of the nearest RPD lesion was 5.08 ± 1.40% compared with 3.33 ± 1.07% between 1 and 3 pixels of the nearest control RPD lesion (P < 0.05). This study identified significantly more RPD lesions on IR compared with SDD lesions on en face spectral domain optical coherence tomography and found that a large majority of SDD (>90% of lesions) were >30 μm away from the nearest RPD. Together, our findings indicate that RPD and SDD are two entities that are only occasionally topographically associated, suggesting that at some stage in their development, they may be pathologically related.

PREVALENCE OF SUBTYPES OF RETICULAR PSEUDODRUSEN IN NEWLY DIAGNOSED EXUDATIVE AGE-RELATED MACULAR DEGENERATION AND POLYPOIDAL CHOROIDAL VASCULOPATHY IN KOREAN PATIENTS.

To evaluate the prevalence and characteristics of subtypes of pseudodrusen in newly diagnosed exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). This retrospective cross-sectional study included 321 eyes of 321 patients who were newly diagnosed with exudative AMD or PCV. Reticular pseudodrusen was classified into dot pseudodrusen and ribbon pseudodrusen; the prevalence of each subtype was estimated and compared between exudative AMD excluding retinal angiomatous proliferation (RAP), PCV, and RAP. Patient age and choroidal thickness were compared between patients with dot pseudodrusen only and those with ribbon pseudodrusen. The prevalence of reticular pseudodrusen was 13.9% (15 of 108 eyes) in exudative AMD excluding RAP, 3.4% (6 of 175 eyes) in PCV, and 68.4% (27 of 38 eyes) in RAP. Among the eyes with pseudodrusen, dot pseudodrusen and ribbon pseudodrusen were noted in 100% and 40.0%, respectively, in exudative AMD excluding RAP, 100% and 16.7%, respectively, in PCV, and 96.2% and 69.2%, respectively, in RAP. Ribbon pseudodrusen was more frequently observed in RAP (P = 0.032). Patients with ribbon pseudodrusen were significantly older (77.3 ± 6.6 years vs. 72.9 ± 8.1 years, P = 0.042) than those with dot pseudodrusen only. The markedly higher incidence of ribbon pseudodrusen in RAP may suggest possible influence of ribbon pseudodrusen on the development of RAP.

Phenotype Characteristics of Fellow Eyes in Patients With Early Onset of Neovascular Age-Related Macular Degeneration.

To investigate phenotype characteristics of fellow eyes in patients with early onset of neovascular age-related macular degeneration (NVAMD). Patients with new-onset unilateral NVAMD between 50 and 65 years (n = 57, early-onset choroidal neovascularization [CNV] group) or >80 years (n = 47, late-onset CNV group) or with nonneovascular AMD (n = 98, no-CNV group) were included. Fellow eyes in both CNV groups and the eyes with the more severe AMD staging in the no-CNV group were used to evaluate number and size of macular drusen, extramacular drusen (EMD), pigmentary abnormalities, and retinal pigment epithelium (RPE) atrophy on color photographs and hyperreflective dots (HRD) and reticular pseudodrusen (RPD) on spectral-domain optical coherence tomography (SDOCT) scans. Regression analysis was used to compare groups. Occurrence of >20 macular drusen was more frequent in the early-onset CNV group than the late-onset CNV group (odds ratio [OR] 2.93; P = 0.01) or the no-CNV group (OR 2.17; P = 0.02). Retinal pigment epithelium atrophy, RPD, and HRD appeared less frequently in the early-onset CNV group than in the late-onset CNV group (RPE atrophy: OR 0.11; P = 0.005; RPD: OR 0.04; P = 9.38 × 10⁻¹⁰, HRD: OR 0.30; P = 0.004) and no-CNV group (RPE atrophy: OR 0.12; P = 0.005; RPD: OR 0.40, P = 0.03, HRD: not significant). No differences were detected regarding presence of large drusen, pigmentary abnormalities, and EMD. A large number of macular drusen in the fellow eye appeared to be characteristic for early onset of NVAMD, whereas RPE atrophy, HRD, and RPD were more frequently present in AMD patients > 80 years. Prospective trials with patients converting to NVAMD are required to further analyze morphologic characteristics for early versus late development of advanced AMD.

Two-year results of combined intravitreal ranibizumab and photodynamic therapy for retinal angiomatous proliferation.

The aim of this study was clarify the efficacy of combination therapy of intravitreal ranibizumab (IVR) injections and photodynamic therapy (PDT) in patients with symptomatic retinal angiomatous proliferation (RAP) over 24 months. We retrospectively reviewed 37 naïve eyes of 31 patients treated with three consecutive monthly IVR injections (0.5 mg/0.05 ml) and PDT and followed for at least 24 months. The mean logarithm of the minimum angle of resolution best-corrected visual acuity levels improved significantly (P < 0.0001) from 0.63 at baseline to 0.39 at 24 months. Geographic atrophy (GA) involving the fovea developed in nine (24%) eyes, with a significant (P = 0.036) decrease in VA at 24 months and a high (100%) prevalence of reticular pseudodrusen (RPD) at baseline. Complete occlusion of the retinal–retinal anastomosis seen in 35 eyes was achieved in 33 eyes at month 24. The central retinal thickness decreased significantly (P < 0.0001) from 415 to 129 μm at 24 months. The mean number of treatments during 24 months was 2.5 PDT and 5.5 IVR injections. Combination therapy comprising IVR injections and PDT is generally effective in maintaining or improving VA and retinal morphology within 2 years in eyes with RAP, except for eyes with baseline RPD, which are likely to develop GA in the fovea resulting in reduced VA.

Choroidal maps in non-exudative age-related macular degeneration

PurposeTo compare choroidal thickness maps (CMs) in patients with non-exudative age-related macular degeneration (AMD) and control subjects using swept source optical coherence tomography (Swept-OCT).MethodsCMs were automatically measured in the different...

Prevalence of reticular pseudodrusen in eyes with newly presenting neovascular age-related macular degeneration.

To use multimodal imaging to evaluate the prevalence of reticular pseudodrusen (RPD) in eyes with newly presenting neovascular age-related macular degeneration (nAMD) in a UK population and explore associations with RPD and angiographic subtypes of nAMD. A retrospective review of all spectral-domain optical coherence tomography, color fundus photographs, red-free and blue channel images, and fundus fluorescein angiograms of 202 consecutive patients who presented to a rapid access macular clinic over a 4-year period was performed. All images were graded by at least 2 ophthalmologists for the presence of RPD and choroidal neovascular membrane (CNV) subtypes. A total of 231 consecutive eyes were studied, of which 131 (56.7%) were in women. Of these, 51 eyes with CNV (22.1%) had identifiable RPD, with one or more imaging methods in that eye. A total of 30.3% of patients with newly presenting CNV in either or both eyes had identifiable RPD. The RPD were bilateral in 85.4% of patients and were identified more commonly in women than men (72.5% vs 27.5%), a difference that reached statistical significance (p = 0.011). No association between RPD and any particular CNV subtype was demonstrated, including for retinal angiomatous proliferations (RAP). Reticular pseudodrusen have a high prevalence in eyes presenting with nAMD (22.1%), although at rates much lower than that of conventional drusen. They are largely a bilateral finding, occurring more frequently in women. Unlike other previous reports, we found no difference in their occurrence between the different subtypes of CNV including RAPs.