The effect of topical 1 % atropine on ocular dimensions and diurnal rhythms of the human eye.

The effect of topical 1 % atropine on the diurnal rhythms of the human eye was investigated. Participants wore an activity monitor on Days 1-7. A set of measures (epochs) encompassing intraocular pressure (IOP), ocular biometry, and retinal imaging were obtained on Day 7 (baseline), followed by eight epochs on Day 8, and one on Day 9 from both eyes of healthy participants (n = 22, 19-25 years). The sleep time of participants (collected via actigraphy) was used as a reference in scheduling epochs. Topical 1 % atropine was instilled in the dominant eye on Day 8, 2 h after habitual wake time, using the fellow eye as control (paired-eye design). Sinusoids with a 24-h period were fitted to the data, and a non-linear mixed-effects model was used to estimate rhythmic statistics. There were no interocular differences in any of the measured parameters at baseline. Comparing pre- versus post-atropine in treated eyes revealed lower IOP, deeper anterior chamber (ACD), decreased crystalline lens thickness and shorter axial length (AL). The same trends were observed when comparing atropine-treated versus fellow control eyes, except for IOP and AL (no differences). Both atropine-treated and fellow control eyes showed significant diurnal variations in all ocular parameters, with atropine-treated eyes revealing larger AL and retinal thickness amplitudes, smaller vitreous chamber depth (VCD) amplitudes, and a significant phase advancement for ACD and VCD. There were no interocular differences in choroidal thickness rhythms. In conclusion, while ocular diurnal rhythms persisted after instillation of 1 % atropine, many rhythmic parameters were altered.

Seasonal and Annual Change in Physiological Ocular Growth of 7- to 11-Year-Old Norwegian Children.

Purpose: To investigate seasonal and annual change in physiological eye growth in Norwegian school children. Methods: Measurements of ocular biometry, non-cycloplegic spherical equivalent autorefraction (SER), and choroidal thickness (ChT) were obtained for 92 children (44 females) aged 7 to 11 years at four time points over a year (November 2019-November 2020). Seasons (3- and 5-month intervals) were classified as winter (November-January), winter-spring (January-June), and summer-autumn (June-November). Cycloplegic SER was obtained in January and used to group children. The seasonal and annual changes were tested with a linear mixed-effects model (P values were adjusted for multiple comparisons). Results: All the children experienced annual ocular growth, irrespective of SER, but less so during the summer-autumn. The baseline SER was lower (P < 0.001), axial length (AL) was longer (P < 0.038), and choroids were thicker in 10- to 11-year-old than 7- to 8-year-old mild hyperopes (P = 0.002). Assuming mild hyperopes (n = 65) experience only physiological eye growth, modeling revealed seasonal and annual increases in AL across sex and age (P < 0.018), with less change during the summer-autumn than winter-spring. The 7- to 8-year-olds had a larger decrease annually and over winter-spring in SER (P ≤ 0.036) and in ChT over winter-spring than the 10- to 11-year-olds (P = 0.006). Conclusions: There were significant seasonal and annual changes in AL in children who had physiological eye growth irrespective of age within this cohort. Annual changes in SER and seasonal choroidal thinning were only observed in 7- to 8-year-old children. This indicates continued emmetropization in 7- to 8-year-olds and a transition to maintaining emmetropia in 10- to 11-year-olds.

Rod and Cone Dark Adaptation in Congenital Aniridia and Its Association With Retinal Structure.

Purpose: To characterize the association between dark-adapted rod and cone sensitivity and retinal structure in PAX6-related aniridia. Methods: Dark-adaptation curves were measured after a 5-minute exposure to bright light with red (625 nm) and green (527 nm) 2° circular light stimuli presented at ≈20° temporal retinal eccentricity in 27 participants with aniridia (nine males; 11-66 years old) and 38 age-matched healthy controls. A two-stage exponential model was fitted to each participant's responses to determine their cone and rod thresholds over time. The thicknesses of macular inner and outer retinal layers were obtained from optical coherence tomography images in 20 patients with aniridia and the 38 healthy controls. Aniridia-associated keratopathy (AAK) grade (0-3) and lens opacities were quantified by clinical examination of the anterior segment. Results: The rod-cone break time was similar between patients with aniridia and healthy controls. Dark-adapted cone and the rod thresholds were higher in aniridia compared with healthy controls. In aniridia, foveal outer retinal layer thickness correlated with both final cone and rod thresholds. A multiple regression model indicated that foveal outer retinal layer thickness and age were the main explanatory variables to predict both final cone and rod thresholds in aniridia when the AAK grade was 2 or less. Conclusions: The results show that both rod- and cone-related functions are affected in PAX6-related aniridia and suggest that retinal anatomical and physiological changes extend beyond the area commonly studied in this condition: the central macula.

Comparing ocular biometry and autorefraction measurements from the Myopia Master with the IOLMaster 700 and the Huvitz HRK-8000A autorefractor.

PURPOSE: To compare axial length (AL) and corneal radius (CR) measured with the Oculus Myopia Master and the Zeiss IOLMaster 700, and cycloplegic refractive error measured with the Myopia Master and the Huvitz Auto Ref/Keratometer (HRK-8000A). METHODS: The study included both eyes of 74 participants (16 male), with a mean (SD) age of 22.8 (3.7) years. The parameters indicated were measured under cycloplegia with these instruments: Myopia Master (AL, CR and refractive error), IOLMaster 700 (AL and CR) and HRK-8000A (refractive error and CR). Bland-Altman plots with mixed effects 95% limits of agreement (LoA) and corresponding 95% confidence intervals were used to assess the agreement in ocular biometry between the Myopia Master and the IOLMaster 700, and for refractive error between the Myopia Master and the HRK-8000A. RESULTS: The analysis included 139 eyes, of which 52 were myopic (spherical equivalent refractive error, SER ≤ -0.50 D), 32 emmetropic and 55 hyperopic (SER ≥ 0.50 D). The 95% LoA for AL between the Myopia Master and IOLMaster 700 was -0.097 to 0.089 mm. There was no mean difference in AL [mean (SD) = -0.004 (0.047) mm, p = 0.34]. There was a significant difference in mean CR, with that measured with the Myopia Master being flatter than that found with the IOLMaster 700 [0.035 (0.028) mm, p < 0.001]. The 95% LoA for CR was -0.02 to 0.09 mm. Compared with HRK-8000A, the Myopia Master measured a significantly more negative SER [-0.19 (0.33) D, p < 0.001], with 95% LoA of -0.86 to 0.46 D. CONCLUSION: The LoA for measurements of SER, CR and AL when comparing the Myopia Master with the HRK-8000A and the IOLMaster 700 were wider than deemed acceptable for making direct comparisons. This indicates that the instruments cannot be used interchangeably in clinical practice or research.

Seasonal Variation in Diurnal Rhythms of the Human Eye: Implications for Continuing Ocular Growth in Adolescents and Young Adults.

Purpose: To investigate the diurnal rhythms in the human eye in winter and summer in southeast Norway (latitude 60°N). Methods: Eight measures (epochs) of intraocular pressure, ocular biometry, and optical coherence tomography were obtained from healthy participants (17-24 years of age) on a mid-winter's day (n = 35; 6 hours of daylight at solstice) and on a day the following summer (n = 24; 18 hours of daylight at solstice). Participants wore an activity monitor 7 days before measurements. The epochs were scheduled relative to the individual's habitual wake and sleep time: two in the day (morning and midday) and six in the evening (every hour until and 1 hour after sleep time). Saliva was collected for melatonin. A linear mixed-effects model was used to determine significant diurnal variations, and a sinusoid with a 24-hour period was fitted to the data with a nonlinear mixed-effects model to estimate rhythmic statistics. Results: All parameters underwent significant diurnal variation in winter and summer (P < 0.002). A 1-hour phase advance was observed for melatonin and ocular axial length in the summer (P < 0.001). The degree of change in axial length was associated with axial length phase advance (R2 = 0.81, P < 0.001) and choroidal thickening (R2 = 0.54, P < 0.001) in summer. Conclusions: Diurnal rhythms in ocular biometry appear to be synchronized with melatonin secretion in both winter and summer, revealing seasonal variation of diurnal rhythms in young adult eyes. The association between axial length and seasonal changes in the phase relationships between ocular parameters and melatonin suggests a between-individual variation in adaptation to seasonal changes in ocular diurnal rhythms.

Laboured reading and musculoskeletal pain in school children - the role of lifestyle behaviour and eye wear: a cross-sectional study.

BACKGROUND: Lifestyle behaviour in children and adolescents has become increasingly sedentary and occupied with digital work. Concurrently, there has been an increase in the prevalence of headache, neck- and low back pain, which are leading causes of disability globally. Extensive near work and use of digital devices are demanding for both the visual system and the upper body head-stabilizing musculature. Uncorrected vision problems are present in up to 40% of Nordic school children, and a lack of corrective eye wear may cause eyestrain, musculoskeletal pain and headache. The aim of this study was to investigate associations between laboured reading, musculoskeletal pain, uncorrected vision, and lifestyle behaviours in children and adolescents. METHODS: This was a cross-sectional study with a total of 192 Norwegian school children aged 10-11 and 15-16 years. As a part of a school vision testing program, the children completed an online questionnaire about general and ocular health, socioeconomic status, academic ambition, near work and related symptoms, upper body musculoskeletal pain, and physical and outdoor activities. RESULTS: The 15-16-year-olds had a more indoor, sedentary, digital-based lifestyle with higher academic demands, compared with the 10-11-year-olds. Concurrently, reading became more laboured and upper body musculoskeletal pain increased with age. Girls reported more symptoms, higher academic ambitions, and more time spent on schoolwork and reading, compared with boys. Non-compliance in wearing prescribed eye wear (glasses or contact lenses), increased use of near digital devices, and experiencing visual stress (glare) were positively associated with laboured reading and upper body musculoskeletal pain. CONCLUSIONS: A screen-based lifestyle with high academic demands challenges the ability to sustain long hours of static, intensive near work. Extensive near work tires the visual system and upper body musculature and provokes laboured reading and musculoskeletal pain symptoms. This study emphasizes the importance of regular eye examinations in school children, and the need to raise awareness among children, parents, and school- and health personnel about the importance of optimal vision and visual environment for academic performance and health.

Human Foveal Cone and RPE Cell Topographies and Their Correspondence With Foveal Shape.

Purpose: To characterize the association between foveal shape and cone and retinal pigment epithelium (RPE) cell topographies in healthy humans. Methods: Multimodal adaptive scanning light ophthalmoscopy and optical coherence tomography (OCT) were used to acquire images of foveal cones, RPE cells, and retinal layers in eyes of 23 healthy participants with normal foveas. Distributions of cone and RPE cell densities were fitted with nonlinear mixed-effects models. A linear mixed-effects model was used to examine the relationship between cone and RPE inter-cell distances and foveal shape as obtained from the OCT scans of retinal thickness. Results: The best-fit model to the cone densities was a power function with a nasal-temporal asymmetry. There was a significant linear relationship among cone and RPE cell spacing, foveal shape, and foveal cell topography. The model predictions of the central 10° show that the contributions of both the cones and RPE cells are necessary to account for foveal shape. Conclusions: The results indicate that there is a strong relationship between cone and RPE cell spacing and the shape of the human adolescent and adult fovea. This finding adds to the existing evidence of the critical role that the RPE serves in fetal foveal development and through adolescence, possibly via the imposition of constraints on the number and distribution of foveal cones.

The Relationship Between Perifoveal L-Cone Isolating Visual Acuity and Cone Photoreceptor Spacing-Understanding the Transition Between Healthy Aging and Early AMD.

Background: Age-related macular degeneration (AMD) is a multifactorial degenerative disorder that can lead to irreversible loss of visual function, with aging being the prime risk factor. However, knowledge about the transition between healthy aging and early AMD is limited. We aimed to examine the relationship between psychophysical measures of perifoveal L-cone acuity and cone photoreceptor structure in healthy aging and early AMD. Methods and Results: Thirty-nine healthy participants, 10 with early AMD and 29 healthy controls were included in the study. Multimodal high-resolution retinal images were obtained with adaptive-optics scanning-light ophthalmoscopy (AOSLO), optical-coherence tomography (OCT), and color fundus photographs. At 5 degrees retinal eccentricity, perifoveal L-cone isolating letter acuity was measured with psychophysics, cone inner segment and outer segment lengths were measured using OCT, while cone density, spacing, and mosaic regularity were measured using AOSLO. The Nyquist sampling limit of cone mosaic (N c ) was calculated for each participant. Both L-cone acuity and photoreceptor inner segment length declined with age, but there was no association between cone density nor outer segment length and age. A multiple regression showed that 56% of the variation in log L-cone acuity was accounted for by N c when age was taken into account. Six AMD participants with low risk of progression were well within confidence limits, while two with medium-to-severe risk of progression were outliers. The observable difference in cone structure between healthy aging and early AMD was a significant shortening of cone outer segments. Conclusion: The results underscore the resilience of cone structure with age, with perifoveal functional changes preceding detectable changes in the cone photoreceptor mosaic. L-cone acuity is a sensitive measure for assessing age-related decline in this region. The transition between healthy aging of cone structures and changes in cone structures secondary to early AMD relates to outer segment shortening.

PAX6 Genotypic and Retinal Phenotypic Characterization in Congenital Aniridia.

Purpose: To investigate the association between PAX6 genotype and macular morphology in congenital aniridia. Methods: The study included 37 participants (15 males) with congenital aniridia (aged 10-72 years) and 58 age-matched normal controls (18 males). DNA was isolated from saliva samples. PAX6 exons, intron/exon junctions, and known regulatory regions were amplified in PCR and sequenced. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect larger deletions or duplications in PAX6 or known cis-regulatory regions. Spectral-domain optical coherence tomography images were acquired and segmented semiautomatically. Mean thicknesses were calculated for inner and outer retinal layers within the macula along nasal and temporal meridians. Results: Mutations in PAX6 or regulatory regions were found in 97% of the participants with aniridia. Foveal hypoplasia was observed in all who had a mutation within the PAX6 gene. Aniridic eyes had thinner outer retinal layers than controls, but with large between-individual variation (mean ± SD, 156.3 ± 32.3 µm vs 210.8 ± 12.3 µm, P < 0.001). Parafoveal and perifoveal inner and outer retinal layers were thinner in aniridia. Participants with mutations in noncoding PAX6 regions had thicker foveal outer retinal layers than those with mutations in the PAX6 coding regions (P = 0.04) and showed signs of postnatal development and maturation. Mutations outside the PAX6 gene were associated with the mildest retinal phenotypes. Conclusions: PAX6 mutations are associated with significant thinning of macular inner and outer retinal layers, consistent with misdirected retinal development resulting in abnormal foveal formation and reduced number of neurons in the macula, with mutations in PAX6 coding regions giving the worst outcome.

Tritan color vision deficiency may be associated with an OPN1SW splicing defect and haploinsufficiency.

Here we present evidence implicating disrupted RNA splicing as a potential cause of inherited tritan color vision. Initially we tested 51 subjects for color vision deficiencies. One made significant tritan errors; the others were classified as normal trichromats. The putative tritan subject was the only one of the 51 subjects found to be heterozygous for an OPN1SW gene mutation that disrupts RNA splicing in an in vitro assay. In order to gather further support for the role of the splicing mutation in tritan color vision, the putative tritan subject's mother and sister were examined. They also made tritan errors and had the same OPN1SW gene mutation.

Characteristics and Utility of Fundus Autofluorescence in Congenital Aniridia Using Scanning Laser Ophthalmoscopy.

Purpose: To investigate fundus autofluorescence (FAF) and other fundus manifestations in congenital aniridia. Methods: Fourteen patients with congenital aniridia and 14 age- and sex-matched healthy controls were examined. FAF images were obtained with an ultra-widefield scanning laser ophthalmoscope. FAF intensity was quantified in the macular fovea and in a macular ring surrounding fovea and related to an internal reference within each image. All aniridia patients underwent an ophthalmologic examination, including optical coherence tomography and slit-lamp biomicroscopy. Results: Mean age was 28.4 ± 15.0 years in both the aniridia and control groups. Fovea could be defined by subjective assessment of FAF images in three aniridia patients (21.4%) and in all controls (P = 0.001). Mean ratio between FAF intensity in the macular ring and fovea was 1.01 ± 0.15 in aniridia versus 1.18 ± 0.09 in controls (P = 0.034). In aniridia, presence of foveal hypoplasia evaluated by biomicroscopy correlated with lack of foveal appearance by subjective analyses of FAF images (P = 0.031) and observation of nystagmus (P = 0.009). Conclusions: Aniridia patients present a lower ratio between FAF intensity in the peripheral and central macula than do healthy individuals. Both subjective and objective analyses of FAF images are useful tools in evaluation of foveal hypoplasia in aniridia.

The Cone Photoreceptor Mosaic in Aniridia: Within-Family Phenotype-Genotype Discordance.

PURPOSE: Investigate in vivo cone photoreceptor structure in familial aniridia caused by deletion in the PAX6 gene to elucidate the complexity of between-individual variation in retinal phenotype. DESIGN: Descriptive case-control study. PARTICIPANTS: Eight persons with congenital aniridia (40-66 yrs) from 1 family and 33 normal control participants (14-69 yrs), including 7 unaffected family members (14-53 yrs). METHODS: DNA was isolated from saliva samples and used in polymerase chain reaction analysis to amplify and sequence exons and intron or exon junctions of the PAX6 gene. High-resolution retinal images were acquired with OCT and adaptive optics scanning light ophthalmoscopy. Cone density (CD; in cones per square millimeter) and mosaic regularity were estimated along nasal-temporal meridians within the central 0° to 5° eccentricity. Horizontal spectral-domain OCT line scans were segmented to analyze the severity of foveal hypoplasia (FH) and to measure retinal layer thicknesses. MAIN OUTCOMES AND MEASURES: Within-family variability in macular retinal layer thicknesses, cone photoreceptor density, and mosaic regularity in aniridia compared with normal control participants. RESULTS: DNA sequencing revealed a known PAX6 mutation (IV2-2delA). Those with aniridia showed variable iris phenotype ranging from almost normal appearance to no iris. Four participants with aniridia demonstrated FH grade 2, 2 demonstrated grade 3 FH, and 1 demonstrated grade 4 FH. Visual acuity ranged from 0.20 to 0.86 logarithm of the minimum angle of resolution. Adaptive optics scanning light ophthalmoscopy images were acquired from 5 family members with aniridia. Foveal CD varied between 19 899 and 55 128 cones/mm2 with overlap between the foveal hypoplasia grades. Cone density was 3 standard deviations (SDs) or more less than the normal mean within 0.5°, 2 SDs less than the normal mean at 0.5° to 4°, and more than 1 SD less than the normal mean at 5° retinal eccentricity. CONCLUSIONS: The results showed considerable variability in foveal development within a family carrying the same PAX6 mutation. This, together with the structural and functional variability within each grade of foveal hypoplasia, underlines the importance of advancing knowledge about retinal cellular phenotype in aniridia.

Prevalence and Possible Factors of Myopia in Norwegian Adolescents.

East Asia has experienced an excessive increase in myopia in the past decades with more than 80% of the younger generation now affected. Environmental and genetic factors are both assumed to contribute in the development of refractive errors, but the etiology is unknown. The environmental factor argued to be of greatest importance in preventing myopia is high levels of daylight exposure. If true, myopia prevalence would be higher in adolescents living in high latitude countries with fewer daylight hours in the autumn-winter. We examined the prevalence of refractive errors in a representative sample of 16-19-year-old Norwegian Caucasians (n = 393, 41.2% males) in a representative region of Norway (60° latitude North). At this latitude, autumn-winter is 50 days longer than summer. Using gold-standard methods of cycloplegic autorefraction and ocular biometry, the overall prevalence of myopia [spherical equivalent refraction (SER) ≤-0.50 D] was 13%, considerably lower than in East Asians. Hyperopia (SER ≥ + 0.50 D), astigmatism (≥1.00 DC) and anisometropia (≥1.00 D) were found in 57%, 9% and 4%. Norwegian adolescents seem to defy the world-wide trend of increasing myopia. This suggests that there is a need to explore why daylight exposure during a relatively short summer outweighs that of the longer autumn-winter.

Color Vision in Aniridia.

Purpose: To assess color vision and its association with retinal structure in persons with congenital aniridia. Methods: We included 36 persons with congenital aniridia (10-66 years), and 52 healthy, normal trichromatic controls (10-74 years) in the study. Color vision was assessed with Hardy-Rand-Rittler (HRR) pseudo-isochromatic plates (4th ed., 2002); Cambridge Color Test and a low-vision version of the Color Assessment and Diagnosis test (CAD-LV). Cone-opsin genes were analyzed to confirm normal versus congenital color vision deficiencies. Visual acuity and ocular media opacities were assessed. The central 30° of both eyes were imaged with the Heidelberg Spectralis OCT2 to grade the severity of foveal hypoplasia (FH, normal to complete: 0-4). Results: Five participants with aniridia had cone opsin genes conferring deutan color vision deficiency and were excluded from further analysis. Of the 31 with aniridia and normal opsin genes, 11 made two or more red-green (RG) errors on HRR, four of whom also made yellow-blue (YB) errors; one made YB errors only. A total of 19 participants had higher CAD-LV RG thresholds, of which eight also had higher CAD-LV YB thresholds, than normal controls. In aniridia, the thresholds were higher along the RG than the YB axis, and those with a complete FH had significantly higher RG thresholds than those with mild FH (P = 0.038). Additional increase in YB threshold was associated with secondary ocular pathology. Conclusions: Arrested foveal formation and associated alterations in retinal processing are likely to be the primary reason for impaired red-green color vision in aniridia.

The Level of Inflammatory Tear Cytokines is Elevated in Congenital Aniridia and Associated with Meibomian Gland Dysfunction.

Purpose: To investigate the tear cytokine profile in congenital aniridia, and correlate cytokine levels with ophthalmologic findings. Methods: We examined 35 patients with aniridia and 21 healthy controls. Tear fluid was collected with Schirmer I test and capillary tubes from each eye, and the concentration of 27 inflammatory cytokines determined using multiplex bead assay. Eyes of all participants were examined with tests for dry eye disease, including evaluation of meibomian glands (meibography). Differences in cytokine levels between the two groups were analyzed, and correlations between cytokine concentrations and ophthalmologic findings in the aniridia group investigated. Results: The concentrations of six tear cytokines were significantly higher in aniridia patients than controls in both eyes, and included interleukin 1ß (IL-1ß), IL-9, IL-17A; eotaxin; basic fibroblast growth factor (bFGF/FGF2); and macrophage inflammatory protein 1α (MIP-1α/CCL3). The ratio between the anti-inflammatory IL-1RA and the proinflammatory IL-1ß was significantly lower in patients than controls in both eyes (P = 0.005 right eye and P = 0.001 left eye). Increasing concentration of IL-1ß, IL-9, IL-17A, FGF2, and MIP-1α correlated with parameters for meibomian gland dysfunction (MGD) in the aniridia group, including increasing atrophy of meibomian glands, and shorter break-up time of the tear film. Conclusions: A number of pro-inflammatory cytokines are significantly elevated in tear fluid from aniridia patients, and correlate with parameters for MGD in aniridia. Increased inflammation of the ocular surface may be a factor in the development of MGD in aniridia patients, and explain the high prevalence of MGD and dry eye disease in these patients.

The genetics of congenital aniridia-a guide for the ophthalmologist.

Congenital aniridia is a rare panocular disease caused by fundamental disturbances in the development of the eye, characterized primarily by hypoplasia of the iris and macula. Severe secondary complications such as keratopathy, cataract, and glaucoma are common and often lead to considerable visual impairment or blindness. Many complications in aniridia patients are difficult to treat and present a challenge for the ophthalmologist. Increasingly, associated nonocular features of the disease are also being recognized. Over the past decades, major steps have been made in the understanding of the genetic basis of aniridia. Moreover, recent studies have prepared the ground for future treatment options based on specific mutations. Therefore, specific knowledge about genetics in aniridia has become more important than ever. We provide an overview of the field of aniridia genetics and its clinical implications.

Multimodal imaging of small hard retinal drusen in young healthy adults.

BACKGROUND: Small hard macular drusen can be observed in the retina of adults as young as 18 years of age. Here, we seek to describe the in vivo topography and geometry of these drusen. METHODS: Retinal images were acquired in young, healthy adults using colour fundus photography, spectral domain optic coherence tomography (SD-OCT), reflectance flood-illuminated adaptive optic ophthalmoscopy (AO flood) and reflectance adaptive optic scanning light ophthalmoscopy (AOSLO) in both confocal and non-confocal split-detection modalities. Small bright yellow hard drusen within a 10 degree radius from the foveal centre were characterised. RESULTS: Small hard drusen were seen on colour photographs in 21 out of 97 participants and 26 drusen in 12 eyes in 11 participants were imaged using the full protocol. Drusen were easily identifiable in all modalities, except a few very small ones, which were not visible on SD-OCT. On AOSLO images, these drusen appeared as round, oval or lobular areas (up to three lobules) of diameter 22-61 µm where cone photoreceptor reflectivity and density was decreased (p=0.049). This was usually associated with discrete thickening of the retinal pigment epithelium (RPE) complex. CONCLUSION: High lateral resolution imaging of small lobular hard retinal drusen suggests formation through the confluence of two or more smaller round lesions. The outline and size of these smaller lesions corresponds to 1-4 RPE cells. Prospective longitudinal studies are needed to determine the ultimate fate of small hard drusen and their potential relation to age-related macular degeneration.