Reticular Pseudodrusen Research Articles

Implications of Analysis Unit on Epidemiology of Multimodal Imaging–Defined Reticular Pseudodrusen

Implications of Analysis Unit on Epidemiology of Multimodal Imaging–Defined Reticular Pseudodrusen

Complement factors and reticular pseudodrusen in intermediate age-related macular degeneration staged by multimodal imaging

ObjectiveSystemic activation of the complement system in intermediate age-related macular degeneration (AMD) is understudied. Moreover, links between the presence of reticular pseudodrusen (RPD) and systemic complement dysregulation have not been...

SCOTOPIC AND FAST MESOPIC MICROPERIMETRY IN EYES WITH DRUSEN AND RETICULAR PSEUDODRUSEN.

To evaluate the feasibility in the clinical practice of a fast and simple mesopic microperimetry examination comparing the retinal sensitivity in eyes with drusen and reticular pseudodrusen by scotopic and mesopic testing. In eyes with only drusen and only reticular pseudodrusen, retinal sensitivity was assessed by mesopic testing and after 35 minutes of dark adaptation by scotopic testing using 2 grids of 6 and 10 stimulus points. Fifteen eyes with drusen and 14 eyes with reticular pseudodrusen were enrolled with mean best-corrected visual acuity of 20/20. In mesopic and scotopic examination, we found significant higher retinal sensitivity of eyes with drusen compared with reticular pseudodrusen (P < 0.001). The mean duration of the examination of mesopic testing was less than 2 minutes, significantly reduced compared with scotopic testing (P < 0.01). Eyes with reticular pseudodrusen presented a significantly reduced retinal sensitivity than eyes with drusen with scotopic and mesopic testing. The different retinal sensitivity between patients was found despite both group presenting good visual acuity. The retinal sensitivity evaluated by mesopic testing may replace the use of scotopic testing and best-corrected visual acuity examination, saving time and providing useful information in the assessment of macular function to identify patients with risk of disease progression.

Impact of Bleaching on Photoreceptors in Different Intermediate AMD Phenotypes.

PurposeTo investigate photoreceptors' structural changes after photobleaching exposure in intermediate age-related macular degeneration (iAMD) eyes with and without reticular pseudodrusen (RPD).MethodsIn this prospective, cross-sectional study, were enrolled iAMD patients and healthy controls. Patients and controls underwent repeated imaging with spectral-domain optical coherence tomography (SD-OCT), at baseline and at three intervals after bleaching, during the subsequent recovery in darkness. Structural changes in photoreceptors were investigated in the foveal region and in four perifoveal areas.ResultsTwenty eyes of 20 iAMD patients (12 with RPD and 8 without RPD) and 15 age-matched healthy controls were enrolled. At baseline, the photoreceptor outer segment (OS) volume was significantly reduced in iAMD eyes with RPD compared with controls, in the foveal and perifoveal regions. In healthy subjects, a precocious increase in OS volume was observed after bleaching in the foveal region, and a rapid recovery to baseline values was recorded. In the perifoveal regions, an increase in OS volume was observed 10 minutes after light onset. In contrast, in iAMD subjects with RPD an altered response to photobleaching, in the foveal and superior and inferior perifoveal regions, was recorded.ConclusionsOur imaging evidences support the hypothesis that dark adaptation is more altered in eyes with RPD. The structural modifications may explain the functional increased damage of the retinal pigment epithelium and photoreceptors reported in eyes with RPD.Translational RelevanceOCT imaging may be used to assess dark adaptation in AMD eyes.

Longitudinal changes in outer nuclear layer thickness in soft drusen and reticular pseudodrusen

BackgroundDrusen are seen in the early and intermediate stages of age‐related macular degeneration. A retrospective, two‐year observational study at a tertiary centre was designed to assess outer nuclear layer thickness in different types of drusen.MethodsPatients over 50-years of age with predominant soft drusen or reticular pseudodrusen were included in the study. Fundus photography, infrared, fundus autofluorescence and spectral domain optical coherence tomography were performed at baseline, years one and two. Outer nuclear layer thickness was measured in the nine Early Treatment Diabetic Retinopathy Study subfields, and the rate of thinning was determined using generalised estimating equations models.ResultsData were analysed from 17 eyes with soft drusen and nine eyes with reticular pseudodrusen. Greater outer nuclear layer thinning was seen overall and in all subfields in reticular pseudodrusen as compared to soft drusen, with statistically significant differences found mostly in superior and nasal subfields of ring 2. The outer nuclear layer was 5–12 μm thinner in eyes with reticular pseudodrusen, and the rate of thinning was greater in eyes with reticular pseudodrusen in the outer superior subfield.ConclusionsOuter nuclear layer thickness is consistently lower in patients with reticular pseudodrusen compared with soft drusen, irrespective of subfield location. These structural findings may contribute to explain the functional abnormalities observed in patients with reticular pseudodrusen.

RETINAL ARTERIAL DILATION IS IMPAIRED IN EYES WITH DRUSEN AND RETICULAR PSEUDODRUSEN.

To analyze static characteristics and dynamic functionality of retinal vessels in eyes with drusen and reticular pseudodrusen (RPD) using dynamic vessel analyzer. Patients with clinical diagnosis of isolated RPD or medium-large drusen and healthy controls were enrolled in the study between July 2016 and May 2018. Participants underwent complete ophthalmologic examination, including enhanced depth imaging structural optical coherence tomography, dynamic retinal vessel analysis, and static retinal vessel analysis. Twenty-eight eyes of 23 patients with drusen (9 men, mean age 77 ± 6 years), 22 eyes of 16 patients with RPD (7 men, mean age: 76 ± 6 years), and 22 eyes of 22 control subjects (11 men, mean age of 75 ± 6 years) were enrolled. Static retinal vessel analysis did not show any significant difference between the three groups for the central retinal artery equivalent (P = 0.11), the central retinal vein equivalent (P = 0.27), and the arteriovenous ratio (P = 0.30). Dynamic vessel analysis showed significantly reduced arterial dilation in eyes with drusen (P = 0.0001) and RPD (P = 0.015) compared with control subjects. No significant difference was seen between drusen and RPD groups (P = 0.32). Dynamic vessel analysis of retinal veins showed no differences between the three groups (P = 0.10). Dynamic vessel analysis in eyes with drusen and RPD revealed an impaired retinal arterial dilation in response to flicker light stimulation, which further supports the relationship between cardiovascular risk and age-related macular degeneration.

CHOROIDAL VASCULARITY INDEX AND CHOROIDAL THICKNESS IN EYES WITH RETICULAR PSEUDODRUSEN.

To evaluate choroidal vascularity index (CVI), choroidal thickness, choroidal volume, and choroidal intensity in subjects with nonneovascular age-related macular degeneration (NNVAMD) with and without reticular pseudodrusen (RPD). We included 60 eyes of 35 subjects with NNVAMD (including 30 eyes of 18 subjects with RPD) and 30 eyes of 17 age-matched healthy individuals from the ongoing Amish Eye study. The choroid was segmented from dense volume spectral domain optical coherence tomography scans and choroidal thickness (microns), choroidal intensity (log units), and choroidal volume (mm) from the entire macula (6 × 6 mm) were computed. A central horizontal B-scan was binarized and the luminal and stromal portions of the choroid were segmented. Choroidal vascularity index (%) was calculated as the ratio of luminal area to total choroid area. Choroidal parameters were compared between the groups by pairwise comparisons using the Student's t-test. The CVI was significantly lower in healthy eyes compared to those with RPD (53.43 ± 8.51 vs. 54.76 ± 4.83, P < 0.001). The CVI was also significantly lower in NNVAMD eyes without RPD compared to those with RPD (50.09 ± 7.51 vs. 54.76 ± 4.83, P = 0.006). There was no difference in CVI between healthy eyes and NNVAMD eyes without RPD (P = 0.84). Choroidal thickness and choroidal volume were significantly higher in NNVAMD without RPD (P < 0.05); and significantly lower in NNVAMD with RPD (P < 0.05) when compared with normal eyes. Choroidal intensity was significantly higher in NNVAMD with RPD when compared with normal eyes (P = 0.02) and NNVAMD eyes without RPD (P = 0.001). Multiple choroidal parameters reflecting the status of the choroidal vasculature and stroma seem to be altered in eyes with RPD compared with both normal eyes and NNVAMD eyes without RPD. These findings may provide insights into the pathophysiology of RPD.

INCIDENCE OF LATE AGE-RELATED MACULAR DEGENERATION IN EYES WITH RETICULAR PSEUDODRUSEN.

To investigate the incidence of late age-related macular degeneration (AMD) over 3 years and risk factors for the development of late AMD in Korean patients having reticular pseudodrusen (RPD). Clinical records of Korean RPD patients with no late AMD at first examination and completion of 3 years of regular follow-up were retrospectively reviewed. All patients underwent complete ocular examinations, including multimodal imaging. Reticular pseudodrusen were classified as a separate lesion different from other early AMD lesions, and RPD were not considered a sign of early AMD. Risk factors for the development of late AMD were assessed. One hundred and ninety-two RPD eyes of 104 patients were included in this study. Mean age of patients was 69.4 ± 8.9 years, and other early AMD lesions were accompanied in 152 eyes (79.2%) at baseline. During 3 years, late AMD occurred in 30 eyes (15.6%); geographic atrophy in 24 eyes (12.5%); and neovascular AMD in 6 eyes (3.1%). Eyes having early AMD at baseline revealed significantly higher incidence for late AMD than those eyes having no early AMD at baseline (18.4% vs. 5%, P = 0.048). Late AMD occurred in 5 eyes (38.5%) from 13 fellow RPD eyes of unilateral late AMD at baseline. In logistic regression analysis, thin choroidal thickness, diffuse distribution of RPD, and the presence of late AMD on fellow eye at baseline were significant risk factors for developing late AMD in RPD eyes. Reticular pseudodrusen eyes revealed various progression rates to late AMD according to AMD status of both eyes. More frequent monitoring should be considered for patients with RPD at risk of progression to late AMD.

Prevalence, Risk, and Genetic Association of Reticular Pseudodrusen in Age-related Macular Degeneration: Age-Related Eye Disease Study 2 Report 21

To determine the prevalence of reticular pseudodrusen (RPD) in eyes with age-related macular degeneration (AMD), assess the role of RPD as an independent risk factor for late AMD development, and evaluate genetic association with RPD. Prospective cohort study. Participants with intermediate AMD in 1 or both eyes enrolled in the Age-Related Eye Disease Study 2 (AREDS2), a 5-year multicenter study of nutritional supplement. Fundus autofluorescence (FAF) images from a subset of AREDS2 participants were evaluated at annual visits for presence of RPD. Six single nucleotide polymorphisms-rs10490924 (ARMS2), rs1061170 (CFH), rs2230199 (C3), rs116503776 and rs114254831 (C2/CFB), and rs943080 (VEGF-A)-and the genetic risk score (GRS) were assessed for association with RPD. Development of late AMD, defined as geographic atrophy (GA) or neovascular AMD (NVAMD), was identified. Prevalence of RPD, odds ratio (OR) of late AMD development, and genetic associations of RPD. The FAF images were evaluated for 5021 eyes (2516 participants). Reticular pseudodrusen were seen in 1186 eyes (24% of eyes, 29% of participants). Prevalence of RPD varied with baseline AREDS AMD severity level: 6% in early AMD (n= 458), 26% in intermediate AMD (n= 2606), 36% in GA (n= 682), and 19% in NVAMD (n= 1246). Mean age of participants with RPD was 79 years (standard deviation [SD], 7) and 75 years (SD, 8) in those without RPD (P < 0.0001). Reticular pseudodrusen were more frequent in female participants (65% RPD vs. 53% no RPD). Odds ratio adjusted for baseline age, gender, race, educational status, smoking, and AMD severity level for 1710 eyes at risk of developing late AMD at the next annual visit was 2.42 (95% confidence interval [CI], 1.80-3.24; P < 0.001) for GA and 1.21 (95% CI, 0.87-1.7; P= 0.26) for NVAMD. Presence of RPD was significantly associated with higher GRS (P < 0.0001) and ARMS2 risk alleles (P < 0.0001) and, at a nominal level, with C3 risk alleles (P= 0.04) and CFH risk alleles (P= 0.048 for homozygotes). Participants with RPD have an increased risk of progression to GA but not NVAMD. ARMS2 risk alleles and higher GRS were associated with the presence of RPD. This study suggests that RPD are an important risk marker and should be included in classification systems used for patient prognosis.

Secondary and Exploratory Outcomes of the Subthreshold Nanosecond Laser Intervention Randomized Trial in Age-Related Macular Degeneration: A LEAD Study Report

To evaluate the secondary and exploratory outcomes of the Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study, a 36-month trial of a subthreshold nanosecond laser (SNL) treatment for slowing the progression to late age-related macular degeneration (AMD) in its early stages. Multicenter, randomized, sham-controlled trial. Two-hundred ninety-two patients with bilateral large drusen. Participants were randomly assigned to receive SNL or sham treatment to the study eye at 6-month intervals. The secondary outcome measure of the LEAD study was the time to development of late AMD, defined by multimodal imaging in the non-study eye. The exploratory outcome measures were the rate of change in best-corrected visual acuity (BCVA), low-luminance visual acuity, microperimetric mean sensitivity, drusen volume in the study and non-study eyes, and participant-reported outcomes based on the Night Vision Questionnaire and Impact of Vision Impairment questionnaire. Progression to late AMD in the non-study eye was not significantly delayed with SNL treatment (hazard ratio, 0.83; 95% confidence interval, 0.40-1.71; P= 0.611). There was no evidence of effect modification based on the coexistence of reticular pseudodrusen; interaction P= 0.065). There was no significant difference between study groups in the rate of change of low-luminance visual acuity, microperimetric mean sensitivity, and drusen volume in the study or non-study eyes, and Night Vision Questionnaire and Impact of Vision Impairment questionnaire scores (all P ≥ 0.167). The rate of BCVA decline was slightly higher for participants in the SNL group compared with the sham treatment group in the study eye (-0.54 and 0.23 letters/year, respectively; P < 0.001) but not the non-study eye (-0.48 and -0.56 letters/year, respectively; P= 0.628). Subthreshold nanosecond laser treatment of one eye did not have an effect on delaying progression to late AMD in the fellow eye and did not, in general, have an impact on the exploratory structural, functional, and participant-reported outcomes.

Retinal sensitivity in angioid streaks

To investigate retinal sensitivity in eyes with angioid streaks (AS). This study was a retrospective observational case series. A total of 13 eyes from 9 patients with AS underwent ophthalmologic examination, including fundus autofluorescence (FAF), spectral domain optical tomography (SD-OCT), and microperimetry. Retinal pigment epithelium (RPE) atrophy was assessed using FAF. Outer retinal atrophy, more specifically, disruption of the ellipsoid zone, was evaluated using SD-OCT images. The association between retinal sensitivity, RPE atrophy or outer retinal atrophy, and patient demographic characteristics or ophthalmologic findings were investigated. The mean area of outer retinal atrophy was 14.5 ± 12.9mm2, significantly larger than the mean area of RPE atrophy (9.0 ± 9.0mm2; P = 0.0028). The average retinal sensitivity in the area of RPE atrophy was 2.4 ± 5.6dB, that in the area of outer retinal atrophy outside RPE atrophy was 14.6 ± 7.5dB, and that in the area without any atrophy was 25.6 ± 5.1dB. Reticular pseudodrusen (RPD) was observed in 5 eyes. Eyes with RPD showed a greater extent of both outer retinal atrophy and RPE atrophy than those without RPD and a greater decrease in mean retinal sensitivity. In eyes with AS, especially in those with RPD, large areas of outer retinal atrophy and RPE atrophy were observed, and the retinal sensitivity in the areas was correspondingly decreased.

Longitudinal Assessment of Rod Function in Intermediate Age-Related Macular Degeneration With and Without Reticular Pseudodrusen.

To evaluate rod function longitudinally in intermediate age-related macular degeneration subjects with reticular pseudodrusen (RPD) and without RPD (AMD). Retinal sensitivities (505 and 625 nm) during dark adaptation, at 14 locations within the central 12° macula were obtained after photobleaching at baseline and 12-month visits. Pointwise sensitivity differences between both stimuli were used to assess static rod function, while rod intercept time (RIT) and rod recovery rate (RRR) were used to evaluate dynamic function. Changes in function over time were compared between groups. A total of 23 controls, 12 AMD, and 13 RPD cases were followed-up. At baseline, the RPD group had significantly worst static and dynamic rod function compared to AMD and control groups. Static function in AMD was similar to controls. Static and dynamic function across the central 12° was consistent in controls; however, it was most impaired at 4° compared to 12° eccentricity in disease groups. Over 12 months, no AMD cases progressed clinically and static function in AMD improved (P ≤ 0.04), but remained unchanged in control and RPD groups (P ≥ 0.17). The RRR for control and RPD groups remained stable, while the AMD group deteriorated, but only at 12° (P = 0.02). The RIT was stable in AMD (P = 0.75) and RPD (P = 0.71) groups but improved in the control group (P = 0.002). A decrease in RRR was detected over 12 months at 12° eccentricity in the AMD group. Evaluating changes in rod function requires testing at multiple locations including the peripheral macula.

Precursors and Development of Geographic Atrophy with Autofluorescence Imaging: Age-Related Eye Disease Study 2 Report Number 18

To describe the sequence of events leading to development of geographic atrophy (GA) in age-related macular degeneration with fundus autofluorescence (FAF) imaging. Post hoc analysis of FAF images from the Age-Related Eye Disease Study2. Fundus autofluorescence images of 120 eyes (109 patients) with incident GA and at least 2 years of preceding FAF images. Images of incident GA were stacked and aligned over FAF images of preceding annual visits. The regions of retina where incident GA developed were assessed on prior years' FAF images. These regions, defined as precursor lesions, were classified into minimal change autofluorescence, predominant hypoautofluorescence (decreased autofluorescence), predominant hyperautofluorescence (increased autofluorescence), and mixed autofluorescence. The natural progression in precursor lesions leading to GA formation and their associations with incident GA size and GA enlargement rate were evaluated. Incident GA area and enlargement rate and precursor pattern frequency. Incident GA had a mean area of 1.00 mm2 (range, 0.15-8.22 mm2) and an enlargement rate of 0.97 mm2/year (standard deviation, 1.66 mm2/year). Predominant hypoautofluorescence was the most common precursor lesion, increasing from 42% to 81% over 3 years before onset of GA. Almost 30% of eyes showed minimal change autofluorescence 3 years before GA. Among the other precursors, 70% progressed to predominant hypoautofluorescence before GA developed. The type of precursor lesions was not associated with incident GA area. Geographic atrophy evolving from minimal change autofluorescence precursor lesions was associated with faster GA enlargement rates compared with other precursor lesion classes. Using image registration, we identified changes in autofluorescence images before the onset of GA. Decreased autofluorescence was the most common change, although minimal changes also were seen in one third of the images. Incident GA that arises from predominantly normal autofluorescence is associated with faster enlargement rates compared with GA arising from abnormal autofluorescence. Faster GA enlargement rates also were associated with incident GA size, area of surround abnormal autofluorescence, and presence of reticular pseudodrusen.

Prevalence and Phenotypes of Age-Related Macular Degeneration in Eyes With High Myopia.

To analyze the frequency and phenotypic variation of AMD in subjects with high myopia (HM), and to describe the clinical course and response to treatment of neovascularization (NV). Patients with HM were identified at five retina tertiary referral centers. Inclusion criteria were myopic patients aged 55 years or more with axial lengths equal or greater than 25.5 mm. A total of 874 eyes from 442 HM subjects older than 55 years were identified and 104 eyes of 54 patients (72 ± 11 years) were included in the study and followed up for 23.5 ± 19.5 months. The estimated AMD frequency in HM subjects over 55 years was 11.9% (95% confidence interval; 9.8%-14.0%). A total of 34 of 104 eyes were diagnosed with drusen, 22 with reticular pseudodrusen (RPD), 28 with both drusen and RPD, and 20 with geographic atrophy. Neovascularization was detected in 52 eyes (50%), and type 1 was the most frequent form (39 eyes, 75%). Overall, NV was treated with 4.6 ± 2.6 anti-VEGF injections. Eyes with treatment-naïve NV at baseline (n = 34) required 3.8 ± 1.5 anti-VEGF injections during the first year of treatment. This exceeded the injection number in the purely myopic population (1.8 to 3.6 injections for the first year). This study provides evidence to suggest that older patients with HM are at a significant risk of the dry and neovascular forms of AMD. NV in eyes with HM and AMD required more injections in the first year compared to NV in HM eyes without AMD.

Retinal findings in carriers of monoallelic ABCC6 mutations

AimBiallelic ABCC6 mutations cause pseudoxanthoma elasticum, a systemic disease characterised by calcification of elastic tissue and a specific retinal phenotype. In this study, we investigated if monoallelic ABCC6 mutations are...

Quantitative proteomic analysis of aqueous humor from patients with drusen and reticular pseudodrusen in age-related macular degeneration

BackgroundTo identify novel biomarkers related to the pathogenesis of dry age-related macular degeneration (AMD), we adopted a human retinal pigment epithelial (RPE) cell culture model that mimics some features of dry AMD including the accumulation of intra- and sub-RPE deposits. Then, we investigated the aqueous humor (AH) proteome using a data-independent acquisition method (sequential window acquisition of all theoretical fragment ion mass spectrometry) for dry AMD patients and controls.MethodsAfter uniformly pigmented polarized monolayers of human fetal primary RPE (hfRPE) cells were established, the cells were exposed to 4-hydroxy-2-nonenal (4-HNE), followed by Western blotting, immunofluorescence analysis and ELISA of cells or conditioned media for several proteins of interest. Data-dependent acquisition for identification of the AH proteome and SWATH-based mass spectrometry were performed for 11 dry AMD patients according to their phenotypes (including soft drusen and reticular pseudodrusen [RPD]) and 2 controls (3 groups).ResultsIncreased intra- and sub-RPE deposits were observed in 4-HNE-treated hfRPE cells compared with control cultures based on APOA1, cathepsin D, and clusterin immunoreactivity. Additionally, the differential abundance of proteins in apical and basal chambers with or without 4-HNE treatment confirmed the polarized secretion of proteins from hfRPE cells. A total of 119 proteins were quantified in dry AMD patients and controls by SWATH-MS. Sixty-five proteins exhibited significantly altered abundance among the three groups. A two-dimensional principal component analysis plot was generated to identify typical proteins related to the pathogenesis of dry AMD. Among the identified proteins, eight proteins, including APOA1, CFHR2, and CLUS, were previously considered major components or regulators of drusen. Three proteins (SERPINA4, LUM, and KERA proteins) have not been previously described as components of drusen or as being related to dry AMD. Interestingly, the LUM and KERA proteins, which are related to extracellular matrix organization, were upregulated in both RPD and soft drusen.ConclusionsDifferential protein expression in the AH between patients with drusen and RPD was quantified using SWATH-MS in the present study. Detailed proteomic analyses of dry AMD patients might provide insights into the in vivo biology of drusen and RPD.

Prevalence of optic disc haemorrhages in an elderly UK Caucasian population and possible association with reticular pseudodrusen-the Bridlington Eye Assessment Project (BEAP): a cross-sectional study (2002-2006).

To determine disc haemorrhage (DH) prevalence in an elderly UK population-the Bridlington Eye Assessment Project (BEAP). Thirty-degree fundus photographs (3549 participants ≥65 years) were graded for DH/macula changes. Glaucoma evaluation included Goldmann tonometry, 26-point suprathreshold visual-fields and mydriatic slit-lamp assessment for glaucomatous optic neuropathy. In all, 3548 participants with photographs in at least one eye. DHs were present in 53 subjects (1.49%), increasing from 1.17% (65- to 69-year age group) to 2.19% (80- to 84-year age group), p = 0.06. DH was found in 9/96 (9.38%) right eyes (RE) with open-angle glaucoma (OAG). Two of twelve RE (16.67%) with normal-tension glaucoma (NTG) had DH. Prevalence in eyes without glaucoma was lower (32/3452, [0.93%]). Reticular pseudodrusen (RPD) occurred in 170/3212 (5.29%) subjects without DH, and 8/131 subjects (6.11%) with OAG. Twenty eyes had NTG, two of whom had RPD (10%) (p = 0.264). Within a logistic regression model, DH was associated with glaucoma (OR 10.2, 95% CI 5.32-19.72) and increasing age (OR 1.05, 95% CI 1.00-1.10, p = 0.03). DH was associated with RPD (p = 0.05) with univariate analysis but this was not statistically significant in the final adjusted model. There was no significant association with gender, diabetes mellitus (DM), hypertension treatment or Age-related Macular Degeneration (AMD) grade. DH prevalence is 1.5% in those over 65 years old and significantly associated with glaucoma and increasing age. There appears to be increased RPD prevalence in eyes with DH and NTG with age acting as a confounding factor. Larger studies are required to fully assess the relationship and investigate a possible shared aetiology of choroidal ischaemia.

Confocal infrared imaging with optical coherence tomography provides superior detection of a number of common macular lesions compared to colour fundus photography.

To compare diagnostic accuracy of confocal infrared reflectance (IR), with and without optical coherence tomography (OCT), to colour fundus photography (CFP) in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) Study. Cross-sectional observational study of participants in NICOLA. CFP, IR and IR/OCT of 640 eyes were graded for hard, soft and reticular pseudodrusen; geographic atrophy; choroidal neovascularisation; naevus; epiretinal membrane; and haemorrhages. Test characteristics (sensitivity and specificity) for each imaging modality with respect to each retinal feature were calculated. With CFP as the reference standard, sensitivity of IR by itself ranged from 75% for RPD to 93.5% for hard drusen and specificity was above 90% for all features except hard drusen (71.7%). For IR combined with OCT, sensitivity ranged from 80% for choroidal neovascularisation to 96.5% for hard drusen. When IR alone was the reference standard, CFP sensitivity was high for naevi (97.5%) but reduced markedly for epiretinal membrane (48.5%). When the combination of IR and OCT was the reference standard, sensitivity for CFP was least for epiretinal membrane (31.5%), low for geographic atrophy and reticular pseudodrusen (77.8% and 76.2% respectively) and high for all other lesion types. Our findings support the use of confocal IR with OCT as a screening tool for a variety of features of macular disease in community optometric practice.

Prevalence of peripapillary choroidal neovascular membranes (PPCNV) in an elderly UK population-the Bridlington eye assessment project (BEAP): a cross-sectional study (2002-2006).

There is paucity of data on the epidemiology of peripapillary choroidal neovascularisartion (PPCNV). Our aim was to determine prevalence of PPCNV in the elderly UK population of Bridlington residents aged ≥65 years. Eyes with PPCNV in the Bridlington eye assessment project (BEAP) database of 3475 participants were analysed. PPCNV outline was drawn, its area measured, and clock-hour involvement of disc circumference recorded. Location and shortest distance from the lesion edge to fovea were recorded. Masked grading for age-related maculopathy (ARM)/reticular pseudodrusen (RPD) within the ETDRS grid was assigned for each eye using a modified Rotterdam scale. Peripapillary retinal pigment epithelial (RPE) changes/drusen were recorded. Visual acuity (VA) and demographic details analysed separately were merged with grading data. PPCNV were identified in ten subjects, and were bilateral in two (20%), a population prevalence of 0.29%, and 0.06% bilaterality. Gender-specific prevalence were 0.36% and 0.19% for females and males, respectively. Age ranged from 66 to 85 years [mean 76.3 (SD 6.4)]. PPCNV were located nasal to disc in 41.7%, measuring 0.46-7.93 mm2 [mean 2.81 mm2 (SD 2.82)]. All PPCNV eyes had peripapillary RPE changes. One subject had no ARM, 1 angioid streaks, and 30% RPD. No direct foveal involvement, or reduced VA attributable to PPCNV was observed. PPCNV were infrequent in this population, more common in females, and often located nasal to the disc, without foveal extension. Peripapillary degenerative changes were universal, and strong association with ARM was observed in eyes with PPCNV. Typically, PPCNV were asymptomatic with VA preservation.

Subthreshold Nanosecond Laser Intervention in Age-Related Macular Degeneration: The LEAD Randomized Controlled Clinical Trial

There is an urgent need for a more effective intervention to slow or prevent progression of age-related macular degeneration (AMD) from its early stages to vision-threatening late complications. Subthreshold nanosecond laser (SNL) treatment has shown promise in preclinical studies and a pilot study in intermediate AMD (iAMD) as a potential treatment. We aimed to evaluate the safety of SNL treatment in iAMD and its efficacy for slowing progression to late AMD. The Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study is a 36-month, multicenter, randomized, sham-controlled trial. Two hundred ninety-two participants with bilateral large drusen and without OCT signs of atrophy. Participants were assigned randomly to receive Retinal Rejuvenation Therapy (2RT®; Ellex Pty Ltd, Adelaide, Australia) SNL or sham treatment to the study eye at 6-monthly intervals. The primary efficacy outcome was the time to development of late AMD defined by multimodal imaging (MMI). Safety was assessed by adverse events. Overall, progression to late AMD was not slowed significantly with SNL treatment compared with sham treatment (adjusted hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.33-1.14; P= 0.122). However, a post hoc analysis showed evidence of effect modification based on the coexistence of reticular pseudodrusen (RPD; adjusted interaction P = 0.002), where progression was slowed for the 222 participants (76.0%) without coexistent RPD at baseline (adjusted HR, 0.23; 95% CI, 0.09-0.59; P= 0.002), whereas an increased progression rate (adjusted HR, 2.56; 95% CI, 0.80-8.18; P= 0.112) was observed for the 70 participants (24.0%) with RPD with SNL treatment. Differences between the groups in serious adverse events were not significant. In participants with iAMD without MMI-detected signs of late AMD, no significant difference in the overall progression rate to late AMD between those receiving SNL and sham treatment were observed. However, SNL treatment may have a role in slowing progression for those without coexistent RPD and may be inappropriate in those with RPD, warranting caution when considering treatment in clinical phenotypes with RPD. Our findings provide compelling evidence for further trials of the 2RT® laser, but they should not be extrapolated to other short-pulse lasers.