Advanced age-related macular degeneration and risk factors in eyes with pachydrusen.

The risk of progression to advanced age-related macular degeneration (AMD) varies depending on the type of drusen. This retrospective longitudinal study included 248 eyes of 156 patients with pachydrusen without advanced AMD at baseline. Macular neovascularization (MNV) and geographic atrophy (GA) were evaluated. Risk factors for progression to advanced AMD were determined using multivariate Cox regression analysis. The mean age at baseline was 65.4 ± 9.1 years, and the mean follow-up duration was 6.40 ± 3.58 years. The mean total number of pachydrusen and macular pachydrusen were 4.10 ± 2.85 and 2.27 ± 1.81 per eye, respectively. Pachydrusen was accompanied by other types of drusen in 4.8% (12 eyes) of eyes at baseline. During follow-up, MNVs occurred in 2.8% (seven eyes), including polypoidal choroidal vasculopathy (PCV six eyes); however, no GA occurred. Regarding risk factors for progression to neovascular AMD, age (p = 0.023) and macular pigmentary changes (p = 0.014) were significantly associated with MNV development. The cumulative incidence of MNV was significantly higher in the group with macular pigmentary changes (17.39% vs. 0.57% at 10 years; p = 0.0005). The number of macular pachydrusen and the presence of MNV in the fellow eye did not show a statistically significant relationship with MNV development. Age and macular pigmentary changes are risk factors for MNV development in the eyes with pachydrusen. Eyes with pachydrusen appear to have a risk profile for advanced AMD that is different from that of AMD eyes with drusen or drusenoid deposits other than pachydrusen.

BILATERAL MACULAR CHOROIDAL ABNORMALITIES WITH DRUSENOID DEPOSITS IN PATIENTS WITH UNILATERAL PERIPHERAL EXUDATIVE HEMORRHAGIC CHORIORETINOPATHY.

PURPOSE: To investigate bilateral macular features on optical coherence tomography in patients with unilateral peripheral exudative hemorrhagic chorioretinopathy (PEHCR). METHODS: In this cross-sectional study, optical coherence tomography features of affected eyes (PEHCR group, n = 30) and unaffected contralateral eyes (contralateral group, n = 30) were investigated. Age-matched and sex-matched patients with polypoidal choroidal vasculopathy (PCV group, n = 51) and healthy controls (normal group, n = 50) were included to compare choroidal thickness, measured at six points apart from the fovea, with the PEHCR group. RESULTS: Subretinal drusenoid deposits were the most common feature in the PEHCR (20%) and contralateral (23%) groups, followed by soft drusen. Although the macular choroid was comparably thin in both the PEHCR and contralateral groups, pachyvessels were also observed. The choroids of the PEHCR group were significantly thinner than those of the normal group at the subfovea and 1-mm temporal to the fovea and considerably thinner than those of the polypoidal choroidal vasculopathy group from 3-mm nasal to 3-mm temporal to the fovea. CONCLUSION: In patients with unilateral PEHCR, bilateral choroidal thinning and drusenoid deposit accumulation were noted in the macula. The pathophysiology of PEHCR may be a rare peripheral complication of age-related macular degeneration with pathologic choroid.

Increased retinal drusen in IgA glomerulonephritis are further evidence for complement activation in disease pathogenesis.

Drusen are retinal deposits comprising cell debris, immune material and complement that are characteristic of macular degeneration but also found in glomerulonephritis. This was a pilot cross-sectional study to determine how often drusen occurred in IgA glomerulonephritis and their clinical significance. Study participants underwent non-mydriatic retinal photography, and their deidentified retinal images were examined for drusen by two trained graders, who compared central drusen counts, counts ≥ 10 and drusen size with those of matched controls. The cohort comprised 122 individuals with IgA glomerulonephritis including 89 males (73%), 49 individuals (40%) of East Asian or Southern European ancestry, with an overall median age of 54 years (34-64), and median disease duration of 9 years (4-17). Thirty-nine (33%) had an eGFR < 60 ml/min/1.73 m2 and 72 had previously reached kidney failure (61%). Overall mean drusen counts were higher in IgA glomerulonephritis (9 ± 27) than controls (2 ± 7, p < 0.001). Central counts ≥ 10 were also more common (OR = 3.31 (1.42-7.73, p = 0.006), and were associated with longer disease duration (p = 0.03) but not kidney failure (p = 0.31). Larger drusen were associated with more mesangial IgA staining (p = 0.004). Increased drusen counts were also present in IgA glomerulonephritis secondary to Crohn's disease but not with Henoch-Schonlein purpura. The finding of retinal drusen in IgA glomerulonephritis is consistent with complement activation and represents a model for better understanding glomerular immune deposition and a supporting argument for treatment with anti-complement therapies.

Heritability and Risk Factors of Incident Small and Large Drusen in the Copenhagen Twin Cohort Eye Study: A 20-Year Follow-Up.

INTRODUCTION: The transition from a normal fundus to one with early drusen (≥20 small hard drusen) to age-related macular degeneration (AMD) in the form of drusen ≥63 µm in diameter is of interest, because small hard drusen may be precursors of large drusen. Study of AMD precursor lesions may provide valuable insight into factors that initiate AMD. Here, the progression of drusen was studied over an interval of 20 years in a population-based twin cohort. METHODS: Single-center, 20-year follow-up of 138 twins include biometry, fundus optical coherence tomography, and fundus photography. Macular characteristics were hierarchically classified as (per eye) (1) <20 small hard drusen, (2) ≥20 small hard drusen, (3) drusen ≥63 µm, or (4) ≥20 small hard drusen combined with drusen ≥63 µm. Additive and dominant genetic effects as well as shared and nonshared environmental effects were analyzed in a bivariate biprobit model with a classic liability-threshold approach and polygenic modeling with random effects. RESULTS: Median participant age was 59 (range 41-66) years. Of 25 (18%) cases of incident macular drusen, 7 had ≥20 small hard drusen, and 18 had drusen ≥63 µm at follow-up, whereas no participant had developed both traits simultaneously. Smoking was associated with incident ≥20 small hard drusen (p = 0.04) and incident drusen ≥63 µm (p = 0.003). Having ≥20 small hard drusen at baseline was associated with incident drusen ≥63 µm at follow-up (p = 0.02). Development of drusen ≥63 µm was attributable to 49% genetic effects and 51% environmental effects. CONCLUSION: The risk of progressing from 0 to 19 small hard macular drusen per eye to having ≥20 small hard drusen or drusen ≥63 µm at follow-up was associated with smoking and genetic predisposition. Having ≥20 small hard drusen in the absence of drusen ≥63 µm at baseline was associated with incident drusen ≥63 µm when examined 20 years later. The study confirms that small hard macular drusen is a forewarning of AMD and that progression to AMD may be hindered by avoidance of smoking.

Retinal drusen counts are increased in inflammatory bowel disease, and with longer disease duration, more complications and associated IgA glomerulonephritis.

Retinal drusen are deposits of inflammatory proteins that are found in macular degeneration and glomerulonephritis and result, in part, from complement activation. This was a cross-sectional observational study of individuals with inflammatory bowel disease (IBD) recruited from a Gastroenterology clinic who underwent non-mydriatic retinal photography. Deidentified images were examined for drusen, and drusen counts and size were compared with matched controls, and examined for clinical associations. The cohort with IBD comprised 19 individuals with ulcerative colitis, 41 with Crohn's disease and three with indeterminate colitis, including 34 males (54%) and an overall median age of 48 (IQR 23) years. Their median IBD duration was 7 (IQR 10) years, median CRP level was 7 (IQR 14) mg/L, and 28 (44%) had complications (fistula, stricture, bowel resection etc.), while 28 with Crohn's disease (68%) had colonic involvement. Drusen counts were higher in IBD than controls (12 ± 34, 3 ± 8 respectively, p = 0.04). Counts ≥ 10 were also more common (14, 22%, and 4, 6%, p = 0.02, OR 4.21, 95%CI 1.30 to 13.63), and associated with longer disease duration (p = 0.01, OR 1.06, 95%CI 1.00 to 1.13), an increased likelihood of complications (p = 0.003, OR 6.90, 95%CI 1.69 to 28.15) and higher CRP levels at recruitment (p = 0.008, OR1.02, 95%CI 1.00 to 1.05). Increased retinal drusen were found in all four individuals with Crohn's disease and IgA glomerulonephritis. IBD and drusen may share pathogenetic mechanisms and underlying risk factors such as complement activation.

Incidence and risk of advanced age-related macular degeneration in eyes with drusenoid pigment epithelial detachment.

To investigate the incidence and risk of advanced age-related macular degeneration (AMD), including geographic atrophy (GA) and macular neovascularization (MNV), in eyes with drusenoid pigment epithelial detachment (PED). Eighty-five eyes with drusenoid PED from 85 patients (77.2 ± 7.0 years, male/female: 44/41) were included in this study. Patients were followed up every 1-3 months via spectral-domain optical coherence tomography (SD-OCT) and color fundus photography. If exudation was observed on SD-OCT, fluorescein and indocyanine green angiography were performed to confirm the MNV subtype accordingly. The maximum follow-up period was 60 months. During the study period, GA developed in 8 eyes while MNV also developed in 8 eyes. The Kaplan-Meier estimator revealed that the cumulative incidence for 60 months was 17.9% and 12.2% for GA and MNV, respectively. In eyes developing MNV, retinal angiomatous proliferation was the most common. Cox regression analysis revealed that baseline PED width was the only factor associated with advanced AMD. (p = 0.0026, Cox regression analysis). The 5-year cumulative incidence of advanced AMD, including GA and MNV, was approximately 30% in eyes with drusenoid PED among the Japanese elderly. A larger baseline PED width was the only risk factor for advanced AMD.

Subthreshold Nanosecond Laser in Age-Related Macular Degeneration: Observational Extension Study of the LEAD Clinical Trial.

PURPOSE: To evaluate the long-term effect of subthreshold nanosecond laser (SNL) treatment on progression to late age-related macular degeneration (AMD). DESIGN: Observational extension study of a randomized, sham-controlled trial. PARTICIPANTS: Two hundred twelve participants with bilateral large drusen. METHODS: The Laser Intervention in the Early Stages of AMD (LEAD) study was a 36-month trial where participants were randomized to receive SNL or sham treatment in 1 eye at 6-monthly intervals up to 30 months. After the completion of the LEAD study, the 2 largest recruiting sites offered remaining participants an opportunity to enroll in a 24-month observational extension study. This study thus examined all participants from these 2 sites who were enrolled in the LEAD study at baseline, including the additional observational data. MAIN OUTCOME MEASURES: Time to develop late AMD, defined on multimodal imaging, between those randomized the SNL or sham treatment. RESULTS: Overall, no significant difference was found in the rate of progression over a 60-month period in those randomized to the SNL compared with the sham group (adjusted hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.36-1.09; P = 0.098), similar to the findings at 36 months in the LEAD Study. However, evidence of treatment effect modification continued to emerge based on the coexistence of reticular pseudodrusen (RPD; P = 0.007, adjusted interaction). Namely, progression was slowed significantly with SNL treatment for those without coexistent RPD (adjusted HR, 0.34; 95% CI, 0.16-0.71; P = 0.004), but it was not significantly different for those with RPD (adjusted HR, 1.81; 95% CI, 0.67-4.88; P = 0.239). CONCLUSIONS: A 24-month observational extension study to the LEAD Study confirmed that SNL treatment did not significantly reduce the overall rate of progression to late AMD in a cohort with intermediate AMD. However, the persistence of a potential beneficial treatment effect in those without coexistent RPD over a longer follow-up duration of an additional 24 months without additional treatment is encouraging. These findings provide further justification for future trials to examine the potential value of SNL treatment for slowing progression in intermediate AMD.

Drusen ooze: Predictor for progression of dry age-related macular degeneration.

BACKGROUND: To evaluate natural history of drusen ooze and its role as a predictor for progression of dry age-related macular degeneration (AMD) longitudinally. METHODS: Multi-centric retrospective observational case series of 72 eyes (72 patients) with dry AMD with a minimum follow-up of 4 years. Drusen types were identified on volume scans on optical coherence tomography (OCT) and were characterized for occurrence of drusen ooze at baseline until last visit. Drusen ooze was defined as hyperreflective dots overlying a collapsing drusen or pseudodrusen, or hyperreflective RPE above drusen or isoreflective dots at the level of outer nuclear layer. The consequent incidence of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA), complete retinal pigment epithelium and outer retinal atrophy (cRORA), and neovascular AMD (nAMD) were evaluated statistically. RESULTS: In total, 72 eyes with a mean follow-up of 68.89 (± 25.57 months) were studied. At presentation, 11 eyes (15.3%) had a single drusen type, whereas 61 eyes (84.7%) had mixed drusen. Reticular pseudodrusen were most common (84.7%) followed by soft drusen (66.6%). Drusen ooze was seen in 47 eyes (65.2%) at presentation. The presence of drusen ooze at baseline (p < 0.01) and baseline best corrected visual acuity (BCVA) (p = 0.04) significantly correlated with development of iRORA and cRORA. In total, 14 eyes progressed from iRORA to cRORA over a mean follow up of 29.14 (± 24.33) months. Odds of progression to iRORA or cRORA were 20.3 times greater for eyes with drusen ooze at baseline (95% C.I., 4.4-94.2). CONCLUSIONS: In dry AMD, drusen ooze is a useful sign for predicting progression to iRORA and cRORA over time.

Influence of vitrectomy on the progression of dry age-related macular degeneration.

PURPOSE: To demonstrate whether pars plana vitrectomy (PPV) changes the progression of dry age-related macular degeneration (AMD) by assessing longitudinal changes in drusen volume over follow-up. METHODS: Dry AMD patients who had undergone unilateral PPV for symptomatic vitreomacular disorders were evaluated for the progression of disease by spectral domain-optical coherence tomography (SD-OCT) features including drusen volume, development of geographic atrophy, or choroidal neovascularization during follow-up. Drusen volume was manually calculated using an image processing software (ImageJ, NIH) on raster SD-OCT scans. Mean change in drusen volume of surgery eyes was compared with values of the fellow eyes of the same subjects (control group). RESULTS: Among 183 eyes with both vitreoretinal disorder and dry AMD, 48 eyes of 24 patients met the inclusion criteria and were included. The mean drusen volume change during a mean of 25.49 ± 23.35 months of follow-up (range: 6.00-86.87 months) was 4.236.899 ± 20.488.913 µm3 in the study eye and 7.796.357 ± 34.798.519 µm3 in the fellow eye (p = 0.297). Best-corrected visual acuity (BCVA) significantly increased from 0.40 ± 0.18 logMAR (≈ 20/50 Snellen equivalent) to 0.32 ± 0.31 (≈ 20/41 Snellen equivalent) after surgery (p = 0.012) in the study group while BCVA remained stable in the control group (0.19 ± 0.34 logMAR [≈ 20/30 Snellen equivalent] at baseline and 0.20 ± 0.31 logMAR [≈ 20/31 Snellen equivalent], p = 0.432). Choroidal neovascularization developed in 1 vitrectomized eye (4.54%) and in 1 eye (4.54%) from the control group during follow-up. CONCLUSION: Vitrectomy did not seem to worsen dry AMD progression; even more visual acuity may improve despite a slight increase in drusen volume following surgery.

Drusen characteristics of type 2 macular neovascularization in age-related macular degeneration.

BACKGROUND: Type 2 macular neovascularization (MNV) is supposed to be a rare condition in age-related macular degeneration (AMD). The main purpose of this study was to assess accompanying factors of type 2 MNV in AMD. METHODS: Retrospective data analysis of eyes previously diagnosed with neovascular AMD in a tertiary eye care center (Medical Retina Unit, Rudolf Foundation Hospital, Vienna, Austria) between June 2008 and December 2017. Drusen subtypes, fibrosis, atrophy and subfoveal choroidal thickness (SFCT) of both eyes in patients with type 2 MNV lesions were categorized based on multimodal imaging. RESULTS: Type 2 MNV was diagnosed in 27 (3.2%) of 835 eyes (749 patients). Drusen characteristics in type 2 MNV were observed as followed: drusen < 63 µm in 2 eyes (7.4%), drusen ≥63 µm in 10 eyes (37%), subretinal drusenoid deposits (SDD) in 8 eyes (29.6%), cuticular drusen in 2 eye (7.4%) and no drusen were evident in 10 eyes (37%). Drusen distribution in 23 fellow eyes was detected as followed: drusen < 63 µm in 2 eyes (8.7%), drusen ≥63 µm in 9 eyes (39.1%), SDD in 5 eyes (21.7%), cuticular drusen in 1 eye (4.3%) and no drusen were evident in 9 eyes (39.1%). Mean SFCT was 140 ± 49 µm in affected eyes and 152 ± 41 µm in the fellow eyes. Patients with drusen or SDD were significantly younger (mean 70.88 ± 6.85, p = 0.04) than patients without deposits (mean 77.40 ± 5.74). CONCLUSIONS: Type 2 MNV remains a rare entity in AMD. It was frequently seen in the absence of drusen, a hallmark of AMD. These findings contribute to the heterogeneity of phenotypes related to pure type 2 lesions.

DRUSEN SUBTYPES AND CHOROIDAL CHARACTERISTICS IN ASIAN EYES WITH TYPICAL NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate the prevalence of pachydrusen, soft drusen, and subretinal drusenoid deposits in eyes with different neovascular age-related macular degeneration (nAMD) subtypes, determine the relationship between each drusen type and the choroidal thickness, and analyze the distinct features of each nAMD subtype according to the drusen type. METHODS: Medical records involving 454 eyes from 454 patients with nAMD were retrospectively reviewed. The prevalence of each drusen type and the choroidal thickness and choroidal characteristics were evaluated according to the nAMD subtype. RESULTS: Pachydrusen were prevalent in the typical nAMD (40.4%) and polypoidal choroidal vasculopathy (47.8%) groups and were not detected in the retinal angiomatous proliferation group. No significant drusen were detected in 24.3% of typical nAMD, 43.3% of polypoidal choroidal vasculopathy, and 0% of retinal angiomatous proliferation groups. Regardless of the nAMD subtype, pachydrusen, soft drusen, and subretinal drusenoid deposits were associated with a thick, moderately thick, and thin choroid, respectively. For eyes with typical nAMD, the prevalence of choroidal vascular hyperpermeability and extrafoveal neovascularization was significantly higher in the pachydrusen group than in the other groups. By contrast, the prevalence of Type 2 neovascularization was significantly lower in the pachydrusen group than in the subretinal drusenoid deposit group (P < 0.001 for all). CONCLUSION: The prevalence of various drusen differed according to the nAMD subtypes, and each drusen type was strongly associated with the choroidal thickness. Typical nAMD showed distinct features according to the accompanying drusen type.

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

PURPOSE: 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. DESIGN: Multicenter, randomized, sham-controlled trial. PARTICIPANTS: Two-hundred ninety-two patients with bilateral large drusen. METHODS: Participants were randomly assigned to receive SNL or sham treatment to the study eye at 6-month intervals. MAIN OUTCOME MEASURES: 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. RESULTS: 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). CONCLUSIONS: 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.

Pachydrusen in polypoidal choroidal vasculopathy in an Indian cohort.

Purpose: To report the prevalence of pachydrusen and their relationship with subfoveal choroidal thickness (SFCT) and large choroidal vessel layer thickness (SF-LCVT) in eyes with polypoidal choroidal vasculopathy (PCV) and their fellow eyes. Methods: The case records of 50 patients (99 eyes; 59 PCV and 40 fellow eyes) were retrospectively analyzed for the presence of pachydrusen and other drusen types such as soft drusen. The diagnosis was established using colour fundus photography and optical coherence tomography (OCT). SFCT and SF-LCVT were measured and correlated with the different types of drusen. Results: The mean age of the study cohort was 62.26 ± 10.67 years and included 27 males and 23 females. Pachydrusen and soft drusen were seen in 14 (PCV: 8 and fellow eyes: 6) and 8 eyes (PCV: 2 and fellow eyes: 6) respectively. The mean SFCT and SF-LCVT in the eyes with and without pachydrusen was not significanty different (280.29 ± 103.11 µ vs. 292.63 ± 87.17 µ; P = 0.63 and 180.57 ± 59.20 vs. 173.73 ± 54.86 µ; P = 0.67, respectively). The pachydrusen were most commonly located near the vascular arcades and showed scattered distribution pattern. Though SFCT and SF-LCVT was lower in the eyes with soft drusen compared to eyes with pachydrusen, it failed to reach statistical significance (SFCT, P = 0.1 and SF-LCVT, P = 0.06). Conclusion: The prevalence of pachydrusen in PCV and their fellow eyes is lower in Indian population suggestive of ethnic variations. SFCT and SF-LCVT was not noted to vary signifcantly in eyes with and without pachydrusen in this study cohort.

Evaluation of coronary artery disease as a risk factor for reticular pseudodrusen.

PURPOSE: Reticular pseudodrusen (RPD) are a risk factor for late age-related macular degeneration (AMD). Associations between RPD and coronary artery disease (CAD) have been reported from small case-control studies. This study investigated the association of RPD within a predominantly CAD cohort. METHODS: A subgroup of subjects from a multicentre randomised controlled trial of CT coronary angiography (CTCA) underwent ultrawide field (UWF) retinal imaging CAD determined by CTCA and was categorised as normal, non-obstructive or obstructive. Specific AMD features in UWF images were graded. Standardised grids were used to record the spatial location of AMD features, including RPD. Multivariate confounder adjusted regression models assessed the association between RPD and CAD. RESULTS: The 534 participants were aged 27-75 years (mean 58±9 years; 425 (80%) ≥50 years) with a male preponderance (56%). Within the study sample, 178 (33%) had no CAD, 351 (66%) had CAD. RPD was detected in 30 participants (5.6%) and bilaterally in 23. Most participants with bilateral RPD had intermediate AMD 17 (74%). After adjustment for potential confounders (age, sex, drusen >125 µm, smoking status), multivariate analysis found no significant association between CAD and RPD (OR 1.31; 95% CI (0.57 to 3.01); p=0.52). A significant association was identified between RPD and intermediate AMD (OR 3.18; 95% CI (1.61 to 6.27); p=0.001). CONCLUSION: We found no evidence to support an association between CAD and RPD. RPD was strongly associated with intermediate AMD features. TRIAL REGISTRATION NUMBER: NCT01149590, Post results.

Prevalence and characteristics of pseudodrusen subtypes in advanced age-related macular degeneration.

PURPOSE: The purpose of our study was to investigate the clinical and genetic characteristics of pseudodrusen subtypes and their incidence in advanced age-related macular degeneration (AMD). METHODS: We studied 84 eyes from 84 patients with pseudodrusen associated with advanced AMD, including typical AMD, polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), and geographic atrophy (GA). Multiple imaging modalities, including color fundus photography, spectral-domain optical coherence tomography (SD-OCT), near-infrared reflectance, and fundus autofluorescence, were employed to diagnose pseudodrusen and its subtypes. Subfoveal choroidal thickness was measured using SD-OCT. Subject eyes were classified into two subtypes, dot-dominant or ribbon-dominant, according to the maximum length of ribbon pseudodrusen. Genotyping was performed for ARMS2 A69S (rs10490924) and CFH I62V (rs800292) variants. RESULTS: The percentage of ribbon-dominant type pseudodrusen was significantly higher in eyes with RAP (69.6%) and GA (78.6%) compared with those with typical AMD (31.1%) (p = .0025 and .0017, respectively). Multivariate logistic regression analysis disclosed that incidence of female patients and coexisting large soft drusen was significantly higher in ribbon- than dot-dominant types (P = 0.014 and P = 0.008, respectively), while age, subfoveal choroidal thickness, and risk allele frequency for both ARMS2 A69S (rs10490924) and CFH I62V (rs800292) were not different between the two pseudodrusen subtypes. CONCLUSIONS: Among eyes with advanced AMD associated with pseudodrusen, ribbon-dominant type pseudodrusen were more prevalent in eyes with GA or RAP and were associated with large soft drusen and female patients.

Photobiomodulation reduces drusen volume and improves visual acuity and contrast sensitivity in dry age-related macular degeneration.

PURPOSE: To evaluate the efficacy of photobiomodulation (PBM) treatment for patients with dry age-related macular degeneration (AMD). METHODS: Assessments on 42 eyes with dry AMD (age related eye disease study (AREDS) 2-4) were conducted. Multiwavelength light emitting diode (LED) light comprising of yellow (590 nm), red (670 nm) and near-infrared (790 nm) bandwidths was applied to subjects' eyes for a treatment course of 3 weeks. Outcome measures were changes in best-corrected visual acuity (BCVA), contrast sensitivity (CS), drusen volume and central drusen thickness. RESULTS: Significant improvement in mean BCVA of 5.90 letters (p < 0.001) was seen on completion of the 3-week treatment and 5.14 letters (p < 0.001) after 3 months. Contrast sensitivity improved significantly (log unit improvement of 0.11 (p = 0.02) at 3 weeks and 3 months (log unit improvement of 0.16 (p = 0.02) at three cycles per degree. Drusen volume decreased by 0.024 mm3 (p < 0.001) and central drusen thickness was significantly reduced by a mean of 3.78 µm (p < 0.001), while overall central retinal thickness and retinal volume remained stable. CONCLUSION: This is the first study demonstrating improvements in functional and anatomical outcomes in dry AMD subjects with PBM therapy. These findings corroborate an earlier pilot study that looked at functional outcome measures. The addition of anatomical evidence contributes to the basis for further development of a non-invasive PBM treatment for dry AMD.

Intravitreal therapies for non-neovascular age-related macular degeneration with intraretinal or subretinal fluid. / Terapias intravítreas en degeneración macular asociada a la edad no neovascular con fluido intrarretiniano o subretiniano.

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=.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. CONCLUSIONS: Cases 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.

Clinical Characteristics and Risk Factors of Extensive Macular Atrophy with Pseudodrusen: The EMAP Case-Control National Clinical Trial.

PURPOSE: To assess the association of clinical and biological factors with extensive macular atrophy with pseudodrusen (EMAP) characterized by bilateral macular atrophy occurring in patients aged 50 to 60 years and a rapid progression to legal blindness within 5 to 10 years. DESIGN: A national matched case-control study. PARTICIPANTS: Participants were recruited in 10 French Departments of Ophthalmology and their associated clinical investigation centers. All 115 patients with EMAP had symptoms before the age of 55 years due to bilateral extensive macular atrophy with a larger vertical axis and diffuse pseudodrusen. Three controls without age-related macular degeneration (AMD) or retinal disease at fundus examination were matched for each patient with EMAP by gender, age, and geographic area (in total 415). METHODS: Subjects and controls underwent an eye examination including color, red-free autofluorescent fundus photographs and spectral-domain optical coherence tomography with macular analysis. The interviews collected demographic, lifestyle, family and personal medical history, medications, and biological data. Associations of risk factors were estimated using conditional logistic regression. MAIN OUTCOME MEASURES: Extensive macular atrophy with pseudodrusen status (cases vs. controls). RESULTS: Extensive macular atrophy with pseudodrusen most frequently affected women (70 women, 45 men). After multivariate adjustment, family history of glaucoma or AMD was strongly associated with EMAP (odds ratio [OR], 2.3, P = 0.008 and OR, 1.5, P = 0.01, respectively). No association was found with cardiac diseases or their risk factors. Mild and moderate kidney disease and higher neutrophil rate were associated with a reduced risk of EMAP (OR, 0.58, P = 0.04; OR, 0.34, P = 0.01; and OR, 0.59, P = 0.003, respectively). On the contrary, eosinophilia (OR, 1.6; P = 0.0002), lymphocytosis (OR, 1.84; P = 0.0002), increased erythrocyte sedimentation rate (OR, 6.5; P = 0.0005), decreased CH50 (P = 0.001), and high plasma C3 level (P = 0.023) were significantly associated with a higher risk of EMAP. CONCLUSIONS: This study documents an association between EMAP and family history of AMD and glaucoma, a clear female predominance, and a systemic inflammatory profile. The reduced CH50 and increased C3 plasma values could reflect a more severe complement pathway dysfunction than in AMD, leading to early pseudodrusen and rapid development of geographic atrophy. There is no association of EMAP with AMD cardiac diseases or cardiac risks, including cigarette smoking.

Drusen Volume as a Predictor of Disease Progression in Patients With Late Age-Related Macular Degeneration in the Fellow Eye.

PURPOSE: Increasing drusen volume was proposed to be a predictor of disease progression in age-related macular degeneration (AMD). In patients with late AMD in one eye, the fellow eyes without neovascularization are known to be at higher risk of developing exudative AMD. We evaluated the relationship between drusen volume in these fellow eyes and their progression to late AMD. METHODS: A retrospective analysis included fellow eyes with drusen associated with nonexudative AMD. All eyes with neovascular AMD were treated with intravitreal ranibizumab, aflibercept, and/or bevacizumab and followed for 2 years. All eyes were scanned with the Cirrus HD-OCT using a 512 × 128 scan pattern. Optical coherence tomography (OCT) data at baseline, month 12, and month 24 were collected using the advanced RPE analysis tool to quantify drusen volume within 3- and 5-mm-diameter circles centered on the fovea. Optical coherence tomography scans were also evaluated for the development of geographic atrophy (GA) or macular neovascularization (MNV). RESULTS: Eighty-nine patients who had neovascular AMD in only one eye were studied. Optical coherence tomography drusen volume in the absence of MNV could be measured in 61 participants (68.5%). After 12 months, 4 eyes (4.5%) developed MNV and 15 eyes (16.9%) developed GA. By 24 months of follow-up, an additional 5 eyes (7.1%) developed MNV and an additional 10 eyes (14.3%) developed GA. At month 24, the eyes that developed GA or MNV had baseline drusen volumes that were significantly larger than in eyes that did not develop late AMD. Patients with a drusen volume over 0.03 mm3 had a greater than 4-fold increased risk for developing late AMD compared with those with lower drusen volumes. CONCLUSIONS: Baseline drusen volume appears to be an important predictor for the development of late AMD within 2 years in eyes that have fellow eyes being actively treated for MNV. This suggests that OCT-derived drusen volume measurements may be a useful biomarker to identify eyes at the highest risk for progression to late AMD.