Retinal Pigment Epithelial Depigmentation Research Articles

Classification and Growth Rate of Chorioretinal Atrophy after Voretigene Neparvovec-Rzyl for RPE65-Mediated Retinal Degeneration

Classify the appearance and quantify the growth rate of chorioretinal atrophy in patients who received voretigene neparvovec-rzyl (VN) for RPE65-mediated retinal degeneration. Multicenter retrospective analysis. Patients who underwent subretinal VN injection at 5 institutions and demonstrated posterior-pole chorioretinal atrophy. Ultrawidefield scanning laser ophthalmoscopy or color fundus photos were assessed before and after subretinal VN. Atrophy was defined as regions with ≥ 2 of the following: (1) partial or complete retinal pigment epithelial depigmentation; (2) round shape; (3) sharp margins; and (4) increased visibility of choroidal vessels. Atrophy was qualitatively classified into different subtypes. All atrophy was manually segmented. Linear mixed-effects models with random slopes and intercepts were fit using atrophy area and square root of atrophy area. Number of eyes with each atrophy pattern, and slopes of linear mixed-effects models. Twenty-seven eyes from 14 patients across 5 centers developed chorioretinal atrophy after subretinal VN. A mean of 5.8 ± 2.7 images per eye obtained over 2.2 ± 0.8 years were reviewed, and atrophy was categorized into touchdown (14 eyes), nummular (15 eyes), and perifoveal (12 eyes) subtypes. Fifteen eyes demonstrated > 1 type of atrophy. Thirteen of 14 patients demonstrated bilateral atrophy. The slopes of the mixed-effects models of atrophy area and square root of atrophy area (estimate ± standard error) were 1.7 ± 1.3 mm2/year and 0.6 ± 0.2 mm/year for touchdown atrophy, 5.5 ± 1.3 mm2/year and 1.2 ± 0.2 mm/year for nummular atrophy, and 16.7 ± 1.8 mm2/year and 2.3 ± 0.2 mm/year for perifoveal atrophy. The slopes for each type of atrophy were significantly different in the square root of atrophy model, which best fit the data (P < 0.05). Chorioretinal atrophy after subretinal VN for RPE65-mediated retinal degeneration developed according to a touchdown, nummular, and/or perifoveal pattern. Perifoveal atrophy grew the most rapidly, while touchdown atrophy grew the least rapidly. Understanding the causes of these findings, which are present in a minority of patients, merits further investigation. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Temporal Topography of Central Serous Chorioretinopathy in the Chinchilla Rabbits Induced by Intravenous Injection of Adrenaline: An in vivo Study.

PurposeTo explore the temporal topography of the chorioretinopathy in an animal model of central serous chorioretinopathy (CSC) induced by intravenous injection of adrenalin in the Chinchilla rabbits.MethodsTen Chinchilla rabbits received a daily intravenous injection of adrenaline at 0.04 mg/kg for 8 weeks. Fluorescence fundus angiography (FFA) and electroretinogram (ERG) were performed every week afterwards to see whether there was fluorescence leakage in the fundus and to evaluate the retinal function. Indocyanine green angiography (ICGA) and optical coherence tomography (OCT) were also conducted to detect the change of choroidal vessels. Finally, the eyes of the rabbits were enucleated to make the retinal sections for histological examination with hematoxylin–eosin (HE) staining.ResultsWithin 8 weeks of the adrenalin administration, 7 out of the 10 rabbits showed different degrees of fluorescence leakage on FFA. The leakage was more obvious during 2–3 weeks after the adrenalin administration. With the progress of disease, the leakage subsided gradually and a scar-like lesion formed. ICGA revealed the local choroidal ischemia and the dilated choroidal vessels. An obvious detachment of retina and an increased thickness of the choroid were found on OCT, which was most obvious 2 weeks after the adrenalin administration (P<0.01). ERG revealed no obvious decline of the b-wave amplitude before and after the adrenalin administration (P>0.05). A circumscribed retinal detachment, the depigmentation of retinal pigment epithelium and enlarged choroidal vessels were shown by the histological examination.ConclusionThe temporal topography of the chorioretinopathy in the Chinchilla rabbits by intravenous injection of adrenaline somewhat mimicked that of the human CSC, which could enhance its application in the exploration for the pathogenesis and the therapeutic measures for human CSC.

Morphological features of macular telangiectasia type 2 in Japanese patients.

This study aimed to demonstrate the clinical course of Japanese patients with macular telangiectasia type 2 (MacTel-2). This retrospective observational case series included 16 eyes of 8 Japanese patients (3 men and 5 women) with MacTel-2. The mean age and follow-up duration was 66.9years and 42.8months, respectively. Differences in best-corrected visual acuity (BCVA), funduscopic macular findings, central macular thickness (CMT), and the length of macular ellipsoid zone (EZ) loss were compared between the initial/baseline and final visits. Optical coherence tomographic changes in CMT by ≥ 20% and in EZ loss by ≥ 20% or ≥ 100μm were defined as improved or worsened. Numerical changes in BCVA and EZ loss during follow-up were not statistically significant. However, the mean CMT at baseline, which was lower than that of healthy control eyes (P < 0.001), significantly increased during follow-up (P = 0.041). A certain proportion of eyes showed improvement in several parameters: funduscopic findings (both parafoveal retinal graying and foveal retinal pigment epithelium depigmentation) in 29% of eyes, CMT in 21% of eyes, and EZ loss in 43% of eyes. The non-negligible proportion of eyes with improved parameters, marked especially by macular EZ loss, suggests that Japanese patients with MacTel-2 have milder clinical features than Caucasian patients reported in the literature.

Central serous chorioretinopathy in elderly subjects: angiographic and tomographic characteristics.

To investigate the angiographic, tomographic, and clinical characteristics of idiopathic central serous chorioretinopathy (CSC) in elderly patients. The patients were divided into two groups according to a cutoff age of 60years at baseline. Patients underwent spectral domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography. Angiographic and tomographic features were compared between the two groups (young vs. elderly group). Of 176 patients, 26 patients (15.1%) were 60years or older. Complete resolution of subretinal fluid after treatment was noted in 72.0% of the elderly group and 90.8% of the young group (P = 0.021). The elderly group showed worse baseline and final vision, more bilateral involvement, and lower male preponderance than the young group (P < 0.05, respectively). The elderly group was also associated with a higher frequency of retinal pigment epithelium depigmentation, foveal thinning, and double-layer sign compared with the young group (P < 0.05, respectively). CSC in elderly patients was associated with a lower resolution of serous detachment, increased impairment of retinal pigment epithelial layers, foveal thinning, and worse visual outcome, suggesting a chronic insult to the choroidal vessels involving more severe damage to the outer retinal layers.

Live porcine thirty days delayed recovery surgery: Qualitative findings with the hypersonic vitrectomy.

IntroductionQualitatively assess the possible delayed structural, macroscopic and microscopic changes in the neuro-retina, retinal vasculature, retinal pigment epithelium (RPE) and optic nerve head (ONH) after pars plana vitrectomy (PPV) surgery using a new hypersonic vitrector (HV).Materials and methodsEight live porcine eyes underwent PPV using either the HV or a conventional pneumatic guillotine vitrector (GV). The un-operated fellow eye from each pig was used as an external control. The pigs were post-operatively kept alive for 30 days before termination and enucleation of the eyes. Prior to enucleation, all eyes underwent examination of the lens and indirect ophthalmoscopy. Enucleated eyes were fixed in formalin, examined macroscopically and processed for histological assessment. Microscopic analysis included assessment of neuro-retina, retinal vasculature, RPE and ONH, as well as observation for any morphological intraocular changes. Comparison was made between: (1) treated and untreated areas of the same eye (internal control) (2) different areas within the same eye operated on using different vitrector settings (3) eyes operated on with the HV and GV (4) eyes receiving surgery and the fellow un-operated eye (external control, same pig).ResultsAll lenses had remained clear at 30 days into the postoperative period. On indirect ophthalmoscopy, the retina had remained attached in all eyes with no visible changes to the neuro-retina, retinal vasculature, RPE or ONH. Two eyes showed localized RPE depigmentation secondary to previously documented intraoperative retinal touch. The Morphological changes in the retinal layers above depigmented RPE were no different from retinal change elsewhere. There were mild and similar microscopic changes observed in the neuro-retina, retinal vasculature, RPE or ONH associated with either the HV or GV PPVs. Preliminary histological findings revealed no significant differences between eyes operated on with the HV and those operated on the GV.DiscussionAt 30 days into the postoperative period, there seemed to be similar morphological changes attributable to the use of HV and GV. Therefore, the HV promises to be a new alternative to the currently commercially available GV for PPV.

Induction of chorioretinopathy by adrenaline injection in different strains of rabbits

Objective To establish a central serous chorioretinopathy(CSC) model on different strains of rabbits by intravenous injection of adrenaline, which may contribute to related researches of CSC. Methods This study was approved by Bioethics Committee of Fourth Military University and complied with Statement for the Use of Animals in Ophthalmic and Visual Research.Fundus fluorescein angiography(FFA) was initially performed on male New Zealand white rabbits (10), Belgium rabbits (5) and Chinchilla rabbits(10) to make sure that the retinas of subjects were normal.For the New Zealand white rabbits, adrenaline was injected via ear vein at a dose of 0.04 mg/kg once per day for the first 8 weeks and followed by a dose of 0.08 mg/kg for the next 4 weeks, while 0.04 mg/kg adrenaline was injected in the same way for 8 weeks in the Belgium rabbits and Chinchilla rabbits.FFA was performed every week after injection of adrenaline to evaluate the fluorescence leakage in ocular fundus.New Zealand white rabbits were sacrificed in 4 (3 rabbits), 8 (3 rabbits) and 12 weeks (4 rabbits) after injection respectively, and Belgium rabbits and Chinchilla rabbits were sacrificed in the 8 weeks after injection.The eyeballs of the rabbits were enucleated to prepare the retinal sections for histopathological examination after hematoxylin-eosin staining.The results of FFA and retinal structure were compared among different strains of rabbits. Results No fluorescence leakage was found by FFA in ocular fundus, and the retinal structure was normal in all the 10 New Zealand white rabbits during the experiment.Fluorescence leakage was found by FFA in 2 Belgium rabbits at 1 week and 2 weeks after injection respectively, and retinal detachment and depigmentation of retinal pigment epithelium (RPE) with an enlarged intercellular space were shown by hematoxylin-eosin staining.For the Chinchilla rabbits, fluorescence leakages were found in 7 rabbits throughout the whole period of adrenaline administration.Circumscribed retinal detachment, depigmentation of RPE with enlarged intercellular space were also found in leakage lesions. Conclusions Repeated intravenous injection of adrenaline can induce CSC-like lesions in colored rabbits but not in albino rabbits. Key words: Adrenaline; Central serous chorioretinopathy; Disease model, animal/drug induction; Fundus fluorescein angiography; New Zealand rabbit; Belgium rabbit; Chinchilla rabbit

Natural History of the Central Structural Abnormalities in Choroideremia: A Prospective Cross-Sectional Study

To describe in detail the central retinal structure of a large group of patients with choroideremia (CHM). A prospective, cross-sectional, descriptive study. Patients (n= 97, age 6-71 years) with CHM and subjects with normal vision (n= 44; ages 10-50 years) were included. Subjects were examined with spectral-domain optical coherence tomography (SD OCT) and near-infrared reflectance imaging. Visual acuity (VA) was measured during their encounter or obtained from recent ophthalmic examinations. Visual thresholds were measured in a subset of patients (n= 24) with automated static perimetry within the central regions (±15°) examined with SD OCT. Visual acuity and visual thresholds; total nuclear layer, inner nuclear layer (INL), and outer nuclear layer (ONL) thicknesses; and horizontal extent of the ONL and the photoreceptor outer segment (POS) interdigitation zone (IZ). Earliest abnormalities in regions with normally appearing retinal pigment epithelium (RPE) were the loss of the POS and ellipsoid zone associated with rod dysfunction. Transition zones (TZs) from relatively preserved retina to severe ONL thinning and inner retinal thickening moved centripetally with age. Most patients (88%) retained VAs better than 20/40 until their fifth decade of life. The VA decline coincided with migration of the TZ near the foveal center. There were outer retinal tubulations in degenerated, nonatrophic retina in the majority (69%) of patients. In general, RPE abnormalities paralleled photoreceptor degeneration, although there were regions with detectable but abnormally thin ONL co-localizing with severe RPE depigmentation and choroidal thinning. Abnormalities of the POS and rod dysfunction are the earliest central abnormalities observed in CHM. Foveal function is relatively preserved until the fifth decade of life. Migration of the TZs to the foveal center with foveal thinning and structural disorganization heralded central VA loss. The relationships established may help outline the eligibility criteria and outcome measures for clinical trials for CHM.

Vitamin D Status and Prevalent Early Age-Related Macular Degeneration in African Americans and Caucasians: The Atherosclerosis Risk in Communities (ARIC) Study.

Vitamin D status has been hypothesized to protect against development of early age-related macular degeneration (AMD) via its anti-inflammatory properties and its possible beneficial influence on blood pressure control. We investigated the association between vitamin D status and prevalent early AMD in a community-based cohort. This was a cross-sectional study. This was a secondary data analysis of already existing data from the Atherosclerosis Risk in Communities Study (ARIC) cohort collected from 1990 to 1995. There were 9,734 (7,779 Caucasians, 1,955 African American) ARIC participants (aged 46 to 70 at visit 2 [1990-1992]) with 25(OH)D data available at visit 2, AMD assessment at visit 3 (1993-1995), and complete covariate data. Vitamin D status was assessed with serum 25-hydroxyvitamin D (25(OH)D) concentrations from bloods drawn at visit 2. Prevalent, early AMD (n=511) was assessed at visit 3 (1993-95) with nonmydriatic retinal photographs of one randomly chosen eye. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for early AMD by categories of 25(OH)D in nmol/L (deficient <30, inadequate 30-<50, and two categories of adequate status: 50-<75 and ≥75). Linear trend was estimated using continuous 25(OH)D concentrations. ORs were adjusted for age, race, and smoking status. We further adjusted for hypertension status to examine if vitamin D status influenced early AMD via its effects on blood pressure. Exploratory analyses of effect modification by age, sex, race and high risk genotypes [Y402H complement factor H (CFH) rs1061170 and the A69S age-related maculopathy susceptibility 2 (ARMS2) rs10490924 polymorphisms] were conducted. The prevalence of early AMD was 5%, and 5% of participants were vitamin D deficient. The adjusted OR (95% CIs) for early AMD among those with adequate (≥75 nmol/L) compared to deficient (<30 nmol/L) vitamin D status was 0.94 (0.59-1.50), p-trend=0.86. Further adjustment for hypertension status did not influence results (OR [95% CI]=0.95 [0.59-1.52], p-trend=0.84). Results did not vary significantly by age, race, sex, early AMD subtype (soft drusen or retinal pigment epithelium depigmentation), or ARMS2 genotype. Results did not vary significantly by CFH genotype in African Americans. The p for multiplicative interaction between 25(OH)D and CFH genotype was 0.06 in Caucasians, but OR [95% CIs] for AMD by vitamin D status were similar in each CFH genotype and not statistically significant. Vitamin D status was not associated with early AMD in this cohort sample.

Age-Related Macular Degeneration and Quality of Life in Latinos: The Los Angeles Latino Eye Study.

This study found evidence of a threshold effect in which the presence of bilateral soft drusen and depigmentation of retinal pigment epithelium was associated with substantially low health-related quality of life (HRQoL) in adult Latinos from the United States. To assess the association of general and vision-specific HRQoL with age-related macular degeneration (AMD), overall and by bilaterality and severity, in adult Latinos. This cross-sectional, population-based study included 4876 participants from the general urban community in 6 US Census tracts in La Puente, California. The data for these analyses were collected as part of a population-based study of ocular diseases in adult Latinos in the Los Angeles Latino Eye Study from February 1, 2000, through May 31, 2003. The analysis was performed from November 2010 to February 2011. Additional analyses were performed in June 2014. Mean-adjusted HRQoL scores and effect sizes. Of the 4876 participants included in the analysis, 4402 (90.3%) had no AMD, and 474 (9.7%) had any AMD, with 453 having early (9.3%) and 21 (0.4%) having late stages of the disease. The mean (SD) age of the cohort was 54.8 (10.7) years. Of the 4876 participants, 2001 (41.0%) were male and 2875 (59.0%) were female. In this cohort of Latinos, participants with AMD had lower vision-specific HRQoL scores. General HRQoL was assessed by the Medical Outcomes Study 12-Item Short-Form Health Survey and self-reported vision-related HRQoL by the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25). Composite NEI-VFQ-25 scores were 59.5 (95% CI, 50.8-68.1) for those with late-stage AMD and 79.4 (95% CI, 72.5-86.1) for those with early-stage AMD, compared with participants without AMD 80.7 (95% CI, 73.9-82.4); P < .001. Several lesions of early AMD were associated with lower NEI-VFQ-25 composite scores and 8 to 10 individual scales. Large effect sizes and lower mean scores were observed for those with late AMD lesions, overall and specifically for geographic atrophy and neovascular AMD, compared with those without AMD. With the use of concatenated bilateral severity levels for AMD, decreases in the NEI-VFQ-25 composite and individual scale scores were observed at the transition from a unilateral to bilateral severity level of 40, which corresponds to having bilateral soft drusen (>125 μm in diameter with drusen area ≥196 350 μm2) and depigmentation of retinal pigment epithelium (slope of -19.17 for the NEI-VFQ-25 composite score). Measures of general health, as assessed by the Medical Outcomes Study 12-Item Short-Form Health Survey, were not affected in this cohort. In this study of adult Latinos, early AMD lesions are associated with lower self-reported, vision-specific HRQoL but not general HRQoL. Severity and bilaterality of AMD are associated with measurably lower HRQoL scores, with the largest difference in scores occurring for individuals with both eyes affected. A concatenated approach to incorporate bilateral severity might be more useful and provide better insight into the association of AMD and HRQoL.

Incidence of Age-Related Macular Degeneration in a Multi-Ethnic United States Population: The Multi-Ethnic Study of Atherosclerosis

To describe the incidence of age-related macular degeneration (AMD) and associated risk factors in 4 racial/ethnic groups (white, black, Hispanic, and Chinese) residing in the United States. Prospective cohort study. A total of 3811 participants, aged 46 to 86 years, from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, with retinal data collected twice, on average, 8 years apart. Fundus images, taken using a digital camera through dark-adapted pupils using a standard protocol and the same equipment at both study visits, were graded centrally for early and late AMD on the basis of drusen size, type and area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. Demographic, clinical, and laboratory measures were included in multivariable regression models to determine their impact on the variation in AMD incidence among racial/ethnic groups. Incident early and late AMD. The overall 8-year age- and sex-standardized incidence of early and late AMD were 4.1% and 2.3%, respectively, with incidence of early and late AMD highest in whites (5.3% and 4.1%, respectively), intermediate in Chinese (4.5% and 2.2%, respectively) and Hispanics (3.3% and 0.8%, respectively), and lowest in blacks (1.6% and 0.4%, respectively). By adjusting for age and sex, blacks had a 70% lower risk of developing early AMD than whites, and this decreased only slightly to a 67% lower risk after multivariable adjustment. By adjusting for age, sex, and race/ethnicity, hyperopia was associated with early AMD (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.20), as was astigmatism (OR, 1.47; 95% CI, 1.00-2.16), but not myopia (P= 0.29). Age, race/ethnicity, current smoking, hyperopia, and AMD-susceptibility genotypes Complement Factor H (CFH) RS1061170 and Age Related Maculopathy Susceptibility 2 (ARMS2) RS3793917 were independently associated with incident early AMD in multivariable models for the combined sample. However, the only statistically significant factor consistently associated with incident early AMD across the 4 racial/ethnic groups was increasing age. Risk factors for late AMD were not assessed because of its low incidence, particularly across racial/ethnic groups. Variation in the incidence of early AMD exists among racial/ethnic groups in the United States and is not explained by the clinical, genetic, and environmental factors included in this study.

Observation on imaging features of two types of fundus autofluorescence and spectral-domain optical coherence tomography in acute central serous chorioretinopathy

Objective To observe the imaging features of short-wave length fundus autofluorescence (SW-AF), near-infrared fundus autofluorescence (NIR-AF)and spectral-domain optical coherence tomograph (SD-OCT) in acute central serous chorioretinopathy (CSC). Methods This is a retrospective observational consecutive case series study. Eighty-two eyes with acute CSC from 76 patients were enrolled in this study.There were 50 males (56 eyes) and 26 females (26 eyes), average age was (41.32±7.37) years old, average course of the disease was (0.47±1.73) months. The routine clinical examinations included best corrected visual acuity, slit lamp microscope, indirect ophthalmoscope, fundus fluorescein angiography (FFA), SW-AF, NIR-AF and SD-OCT. The imaging features of NIR-AF, SW-AF, SD-OCT and FFA in same eye with acute CSC were analyzed comparatively. Results SD-OCT showed retinal pigment epithelium (RPE) detachment corresponding to RPE leakage point on FFA images in all CSC eyes. RPE leakage points in all eyes corresponding to local hypo-NIR-AF, whereas corresponding to normal SW-AF. NIR-AF demonstrated the area of decreased AF corresponding to serous retinal detachment in all eyes, of which, the area of hypo-SW-AF was consistent with that of sensory retinal detachment in 75 eyes. Except for RPE leaking fluorescein in 82 eyes, FFA showed window defects corresponding to clusters of hypo-NIR-AF in 45 eyes, of which, 27 eyes showed hypo-SW-AF appearing concurrently with the locations of window defects of FFA. In 18 eyes, the extent and amount of hypo-SW-AF were less than that of hypo-NIR-AF. Conclusions There was local RPE detachment in all eyes with acute CSC. The locations of sensory retinal detachment, local RPE detachment and RPE depigmentation showed hypo-NIR-AF. The locations of sensory retinal detachment and RPE depigmentation showed hypo-SW-AF in most of acute CSC eyes. Key words: Central serous chorioretinopathy; Tomography, optical coherence; Fluorescein angiography; Diagnostic imaging

The oral iron chelator deferiprone protects against systemic iron overload-induced retinal degeneration in hepcidin knockout mice.

To investigate the retinal-protective effects of the oral iron chelator deferiprone (DFP) in mice lacking the iron regulatory hormone hepcidin (Hepc). These Hepc knockout (KO) mice have age-dependent systemic and retinal iron accumulation leading to retinal degeneration. Hepc KO mice were given DFP in drinking water from age 6 to 18 months. They were then compared to Hepc KO mice not receiving DFP by fundus imaging, electroretinography (ERG), histology, immunofluorescence, and quantitative PCR to investigate the protective effect of DFP against retinal and retinal pigment epithelial (RPE) degeneration. In Hepc KO mice, DFP diminished RPE depigmentation and autofluorescence on fundus imaging. Autofluorescence in the RPE layer in cryosections was significantly diminished by DFP, consistent with the fundus images. Immunolabeling with L-ferritin and transferrin receptor antibodies showed a decreased signal for L-ferritin in the inner retina and RPE cells and an increased signal for transferrin receptor in the inner retina, indicating diminished retinal iron levels with DFP treatment. Plastic sections showed that photoreceptor and RPE cells were well preserved in Hepc KO mice treated with DFP. Consistent with photoreceptor protection, the mRNA level of rhodopsin was significantly higher in retinas treated with DFP. The mRNA levels of oxidative stress-related genes heme oxygenase-1 and catalase were significantly lower in DFP-treated Hepc KO retinas. Finally, ERG rod a- and b- and cone b-wave amplitudes were significantly higher in DFP-treated mice. Long-term treatment with the oral iron chelator DFP diminished retinal and RPE iron levels and oxidative stress, providing significant protection against retinal degeneration caused by chronic systemic iron overload in Hepc KO mice. This indicates that iron chelation could be a long-term preventive treatment for retinal disease involving iron overload and oxidative stress.

Serum carboxymethyllysine, an advanced glycation end product, and age-related macular degeneration: the Age, Gene/Environment Susceptibility-Reykjavik Study.

IMPORTANCE Advanced glycation end products have been implicated in the pathogenesis of age-related macular degeneration (AMD). OBJECTIVE To investigate the relationship between serum carboxymethyllysine (CML), a major circulating advanced glycation end product, and AMD in older adults. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of a population-based sample of 4907 older adults (aged ≥66 years) in the Age, Gene/Environment Susceptibility-Reykjavik Study in Iceland. EXPOSURES Serum CML and risk factors for AMD. MAIN OUTCOMES AND MEASURES Early or late AMD, assessed through fundus images taken through dilated pupils using a 45° digital camera and grading for drusen size, type, area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. RESULTS Of the 4907 participants, 1025 (20.9%) had early AMD and 276 (5.6%) had late AMD. Mean (SD) serum CML concentrations among adults with no AMD, early AMD, and late AMD (exudative AMD and pure geographic atrophy) were 618.8 (195.5), 634.2 (206.4), and 638.4 (192.0) ng/mL, respectively (to convert to micromoles per liter, multiply by 0.00489; P = .07). Log serum CML (per 1-SD increase) was not associated with any AMD (early and late AMD) (odds ratio = 0.97; 95% CI, 0.90-1.04; P = .44) or with late AMD (odds ratio = 0.94; 95% CI, 0.82-1.08; P = .36) in respective multivariable logistic regression models adjusting for age, sex, body mass index, smoking, and renal function. CONCLUSIONS AND RELEVANCE Higher serum CML concentration had no significant cross-sectional association with prevalent AMD in this large population-based cohort of older adults in Iceland.

Retinal Damage in Chloroquine Maculopathy, Revealed by High Resolution Imaging: A Case Report Utilizing Adaptive Optics Scanning Laser Ophthalmoscopy

A 53-year-old Asian woman was treated with hydroxychloroquine and chloroquine for lupus erythematosus. Within a few years, she noticed circle-shaped shadows in her central vision. Upon examination, the patient's visual acuity was 20 / 25 in both eyes. Humphrey visual field (HVF) testing revealed a central visual defect, and fundoscopy showed a ring-shaped area of parafoveal retinal pigment epithelium depigmentation. Fundus autofluorescence imaging showed a hypofluorescent lesion consistent with bull's eye retinopathy. Adaptive optics scanning laser ophthalmoscope (AO-SLO) revealed patch cone mosaic lesions, in which cones were missing or lost. In addition, the remaining cones consisted of asymmetrical shapes and sizes that varied in brightness. Unlike previous studies employing deformable mirrors for wavefront aberration correction, our AO-SLO approach utilized dual liquid crystal on silicon spatial light modulators. Thus, by using AO-SLO, we were able to create a photographic montage consisting of high quality images. Disrupted cone AO-SLO images were matched with visual field test results and functional deficits were associated with a precise location on the montage, which allowed correlation of histological findings with functional changes determined by HVF. We also investigated whether adaptive optics imaging was more sensitive to anatomical changes compared with spectral-domain optical coherence tomography.

Peripheral Autofluorescence and Clinical Findings in Neovascular and Non-neovascular Age-related Macular Degeneration

To characterize peripheral fundus autofluorescence (FAF) abnormalities in patients with age-related macular degeneration (AMD), correlate these with clinical findings, and identify risk factors associated with these FAF abnormalities. Clinic-based, cross-sectional study. A total of 119 consecutive patients: 100 patients with AMD (200 eyes) and 19 patients without AMD (38 eyes). In a prospective study performed at the Doheny Eye Institute, University of Southern California, widefield 200-degree FAF and color images were obtained by the Optos 200Tx Ultra-Widefield device (Optos, Dunfermline, Scotland) using a standardized imaging protocol. The FAF images were captured centered on the fovea, and additional images were captured after steering the field of view inferiorly and superiorly. All FAF and color images were graded independently by 2 masked ophthalmologists with respect to the presence, location, extent, and type of peripheral (defined as outside the central 30 degrees) FAF abnormality. Presence and type of peripheral FAF abnormalities. Peripheral FAF abnormalities were evident in 164 eyes (68.9%), with several distinct FAF patterns identified: granular (46.2%), mottled (34.0%), and nummular (18.1%). A 90% concordance of FAF patterns was observed between both eyes. Abnormal FAF occurred more frequently in neovascular compared with non-neovascular AMD or normal eyes (86% vs. 72.8% vs. 18.4%, respectively, P<0.001). Significant risk factors for peripheral FAF abnormalities were AMD type (neovascular AMD odds ratio [OR], 12.7 and non-neovascular AMD OR, 6.2 compared with normal eyes, P<0.001), older age (OR, 6.5; 95% confidence interval [CI], 2.4-17.8; P<0.001 for the oldest quartile compared with the youngest), and female sex (OR, 4.1; 95% CI, 1.9-8.9; P<0.001). Clinical features on color photography were detected in 174 eyes (73.1%): peripheral drusen (51.7%), retinal pigment epithelium (RPE) depigmentation (34.9%), RPE hyperpigmentation (branching reticular pigmentation) (22.7%), and atrophic patches (16.8%). There was a high correlation between specific FAF and clinical findings: granular FAF with peripheral drusen (P<0.001) and mottled FAF with RPE depigmentation (P<0.001). Several distinct patterns of peripheral FAF abnormalities were observed in 68.9% of patients, with AMD type, female sex, and age being independent risk factors. The peripheral FAF patterns correlate strongly with specific clinical features seen in eyes with AMD. Proprietary or commercial disclosure may be found after the references.

Risk Factors for Four-Year Incidence and Progression of Age-Related Macular Degeneration: The Los Angeles Latino Eye Study

To identify risk factors for 4-year incidence and progression of age-related macular degeneration (AMD) in adult Latinos. Population-based prospective cohort study. Participants, aged 40 or older, from The Los Angeles Latino Eye Study (LALES) underwent standardized comprehensive ophthalmologic examinations at baseline and at 4 years of follow-up. Age-related macular degeneration was detected by grading 30-degree stereoscopic fundus photographs using the modified Wisconsin Age-Related Maculopathy Grading System. Multivariate stepwise logistic regression was used to examine the independent association of incidence and progression of AMD and baseline sociodemographic, behavioral, clinical, and ocular characteristics. Multivariate analyses revealed that older age (OR per decade of age: 1.52; 95% CI: 1.29, 1.85) and higher pulse pressure (OR per 10 mm Hg: 2.54; 95% CI: 1.36, 4.76) were independently associated with the incidence of any AMD. The same factors were associated with early AMD, soft indistinct drusen, and retinal pigmentary abnormalities. Additionally, presence of clinically diagnosed diabetes mellitus was independently associated with increased retinal pigment (OR: 1.66; 95% CI: 1.01, 2.85), and male gender was associated with retinal pigment epithelial depigmentation (OR 2.50; 95% CI: 1.48, 4.23). Older age (OR per decade of age: 2.20; 95% CI: 1.82, 2.67) and current smoking (OR: 2.85; 95% CI: 1.66, 4.90) were independently associated with progression of AMD. Several modifiable risk factors were associated with 4-year incidence and progression of AMD in Latinos. The results suggest that interventions aimed at reducing pulse pressure and promoting smoking cessation may reduce incidence and progression of AMD, respectively.

Prevalence of Age-related Macular Degeneration in Old Persons: Age, Gene/Environment Susceptibility Reykjavik Study

To describe the prevalence and signs of early and late age-related macular degeneration (AMD) in an old cohort. Population-based cohort study. We included 5272 persons aged ≥66 years, randomly sampled from the Reykjavik area. Fundus images were taken through dilated pupils using a 45-degree digital camera and graded for drusen size, type, area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy (GA) using the modified Wisconsin Age-Related Maculopathy Grading System. Age-related macular degeneration in an elderly cohort. The mean age of participants was 76 years. The prevalence of early AMD was 12.4% (95% confidence interval [CI], 11.0-13.9) for those aged 66 to 74 years and 36% (95% CI, 30.9-41.1) for those aged ≥85 years. The prevalence of exudative AMD was 3.3% (95% CI, 2.8-3.8). The prevalence of pure GA was 2.4% (95% CI, 2.0-2.8). The highest prevalence of late AMD was among those aged ≥85 years: 11.4% (95% CI, 8.2-14.5) for exudative AMD and 7.6% (95% CI, 4.8-10.4) for pure GA. Persons aged ≥85 years have a 10-fold higher prevalence of late AMD than those aged 70 to 74 years. The high prevalence of late AMD in the oldest age group and expected increase of elderly people in the western world in coming years call for improved preventive measures and novel treatments.

Ocular Risk Factors for Age-Related Macular Degeneration: The Los Angeles Latino Eye Study

To assess the association between ocular factors and age-related macular degeneration (AMD) in Latinos. Population-based, cross-sectional study of 6357 self-identified Latinos aged 40 years and older. Ophthalmic examination included subjective refraction, measurement of axial length, evaluation of iris color, Lens Opacities Classification System II (LOCS II) grading of cataracts, and stereoscopic macular photographs for AMD lesions. Generalized estimating equation analysis incorporated data from both eyes to estimate odds ratios (OR) adjusted for covariates. After controlling for confounders (age, gender, and smoking), prior cataract surgery was associated with advanced AMD (OR, 2.8; 95% CI, 1.01, 7.8), increased retinal pigment (OR, 1.6; 95% CI, 1.02, 1.5), and retinal pigment epithelial depigmentation (OR, 2.2; 95% CI, 1.1, 4.4). The presence of any lens opacity was associated with soft drusen (OR, 1.2; 95% CI, 1.002, 1.5). Longer axial length (per mm) was associated with decreased odds of soft drusen, increased retinal pigment, and geographic atrophy (GA) (ORs, 0.8 [95% CI, 0.7, 0.9], 0.8 [95% CI, 0.7, 0.9], 0.7 [95% CI, 0.5, 0.9], respectively). Myopia was inversely associated with soft drusen (OR, 0.8; 95% CI, 0.7, 0.99). Lighter-colored irises were associated with GA (OR, 5.0; 95% CI, 1.0, 25.3). Cross-sectional associations of ocular factors such as cataract, cataract surgery, and refractive errors with early AMD lesions found in Latinos are consistent with those in non-Hispanic Whites. Additionally, prior cataract surgery was associated with advanced AMD.

Pulmonary Disease and Age-Related Macular Degeneration

To examine the association of pulmonary symptoms, disease, and function with the incidence of age-related macular degeneration (AMD). Population-based cohort study of persons aged 43 to 86 years at baseline (N = 4926), of whom 3779 participated in 1 or more follow-up examinations. Stereoscopic photographs of the macula were graded to determine the presence of AMD. Existence of emphysema, asthma, and respiratory symptoms was determined from subjects' medical history questionnaires; the peak expiratory flow rate was measured using a Mini-Wright Peak Flow Meter (Clement Clarke International, Harlow, England). Discrete logistic hazard and logistic regression models were used. Incidence and progression of AMD. While controlling for age, sex, and other factors, a history of emphysema at baseline was found to be associated with the 15-year cumulative incidence of increased retinal pigment (odds ratio, 2.08; 95% confidence interval, 1.06-4.06), retinal pigment epithelium depigmentation (2.40; 1.23-4.67), and exudative AMD (3.65; 1.24-10.73). Mild pulmonary symptoms were associated with the 5-year incidence of exudative AMD (odds ratio, 3.83; 95% confidence interval, 1.39-10.58), and the fourth (ie, highest) quartile of pulmonary expiratory flow rate showed a protective effect for progression of AMD among women (0.36; 0.15-0.86). Independent of smoking, a history of emphysema and respiratory symptoms and function are modestly but inconsistently associated with the incidence and progression of AMD.

Risk Factors for Choroidal Neovascularization and Geographic Atrophy in the Complications of Age-Related Macular Degeneration Prevention Trial

To determine risk factors for choroidal neovascularization (CNV) and of geographic atrophy (GA) in eyes with large drusen. Cohort study within a multicenter, randomized clinical trial of laser treatment for the prevention of vision loss from advanced age-related macular degeneration. One thousand fifty-two participants with 10 or more large drusen (>or=125 microm) and visual acuity of 20/40 or better in each eye. At baseline, participants provided a brief medical history. Trained readers evaluated baseline color photographs for drusen characteristics and pigmentary abnormalities. One eye of each participant was assigned to laser treatment and the contralateral eye was assigned to observation. The Complications of Age-Related Macular Degeneration Prevention Trial (CAPT) Reading Center readers identified CNV and endpoint GA from color photographs and fluorescein angiograms obtained during follow-up visits scheduled for 5 or 6 years. Estimates of relative risks (RRs) and 95% confidence intervals (CIs) were obtained from survival analyses of observed and treated eyes, considered separately and combined. Development of CNV and of endpoint GA. Choroidal neovascularization developed in 141 observed eyes and 141 treated eyes, including 57 patients affected bilaterally. Statistically significant risk factors for CNV in the multivariate model for all eyes were older age (RR, 2.81 [95% CI, 1.33-5.94] for >79 years vs. 50-59 years), cigarette smoking (RR, 1.98 [95% CI, 1.16-3.39] for current vs. never), and focal hyperpigmentation (RR, 1.84 [95% CI, 1.22-2.76] for >or=250 microm vs. none). Among eyes free of GA at baseline, endpoint GA developed in 61 observed eyes and in 58 treated eyes, including 29 patients affected bilaterally. Statistically significant risk factors for GA in the multivariate model for all eyes were older age (RR, 6.39 [95% CI, 1.64-24.9] for >79 years vs. 50-59 years), greater retinal area covered by drusen (RR, 5.10 [95% CI, 2.57-10.1] for >or=25% vs. <10%), retinal pigment epithelium (RPE) depigmentation (RR, 2.64 [95% CI, 1.26-5.53), and focal hyperpigmentation (RR, 10.4 [95% CI, 4.51-24.0] for >or=250 microm vs. none). Among CAPT participants, increased age and focal hyperpigmentation were risk factors for the development of CNV and for GA. Cigarette smoking was significantly associated with CNV only, whereas retinal area covered by drusen and RPE depigmentation were associated significantly with GA only.