Insights into the developing fovea revealed by imaging.

Early development of the fovea has been documented by histological studies over the past few decades. However, structural distortion due to sample processing and the paucity of high-quality post-mortem tissue has limited the effectiveness of this approach. With the continuous progress in high-resolution non-invasive imaging technology, most notably optical coherence tomography (OCT) and OCT angiography (OCT-A), in vivo visualization of the developing retina has become possible. Combining the information from histologic studies with this novel imaging information has provided a more complete and accurate picture of retinal development, and in particular the developing fovea. Advances in neonatal care have increased the survival rate of extremely premature infants. However, with enhanced survival there has been an attendant increase in retinal developmental complications. Several key abnormalities, including a thickening of the inner retina at the foveal center, a shallower foveal pit, a smaller foveal avascular zone, and delayed development of the photoreceptors have been described in preterm infants when compared to full-term infants. Notably these abnormalities, which are consistent with a partial arrest of foveal development, appear to persist into later childhood and adulthood in these eyes of individuals born prematurely. Understanding normal foveal development is vital to interpreting these pathologic findings associated with prematurity. In this review, we first discuss the various advanced imaging technologies that have been adapted for imaging the infant eye. We then review the key events and steps in the development of the normal structure of the fovea and contrast structural features in normal and preterm retina from infancy to childhood. Finally, we discuss the development of the perifoveal retinal microvasculature and highlight future opportunities to expand our understanding of the developing fovea.

Parafoveal processing of orthographic, morphological, and semantic information during reading Arabic: A boundary paradigm investigation.

Evidence shows that skilled readers extract information about upcoming words in the parafovea. Using the boundary paradigm, we investigated native Arabic readers' processing of orthographic, morphological, and semantic information available parafoveally. Target words were embedded in frame sentences, and prior to readers fixating them, one of the following previews were made available: (a) Identity preview; (b) Preview that shared the pattern morpheme with the target; (c) Preview that shared the root morpheme with the target; (d) Preview that was a synonym with the target word; (e) Preview with two of the root letters were transposed thus creating a new root, while preserving all letter identities of the target; (f) Preview with two of the root letters were transposed thus creating a pronounceable pseudo root, while also preserving all letter identities of the target; and (g) Previews that was unrelated to the target word and shared no information with it. The results showed that identity, root-preserving, and synonymous preview conditions yielded preview benefit. On the other hand, no benefit was obtained from the pattern-preserving previews, and significant disruption to processing was obtained from the previews that contained transposed root letters, particularly when this letter transposition created a new real root. The results thus reflect Arabic readers' dependance on morphological and semantic information, and suggest that these levels of representation are accessed as early as orthographic information. Implications for theory- and model-building, and the need to accommodate early morphological and semantic processing activities in more comprehensive models are further discussed.

Interpretation of anatomic correlates of outer retinal bands in optical coherence tomography.

By providing the sectioning capability to differentiate individual retinal layers, optical coherence tomography (OCT) is revolutionizing eye disease diagnosis and treatment evaluation. A better understanding of the hyper- and hypo-reflective bands in retinal OCT is essential for accurate interpretation of clinical outcomes. In this article, we summarize the interpretations of clinical OCT and adaptive optics (AO) OCT (AO-OCT) of the outer retina in the human eye, and briefly review OCT investigation of the outer retina in animal models. Quantitative analysis of outer retinal OCT bands is compared to established parameters of retinal histology. The literature review and comparative analysis support that both inner/outer segment (IS/OS) junction and IS ellipsoid zone nonexclusively contribute to the second band; and OS, OS tips, and retinal pigment epithelium apical processes contribute to the third band in conventional OCT. In contrast, AO-OCT might predominantly detect the IS/OS junction and OS tip signals at the second and third bands due to its improved sectioning capability and possible AO effect on the sensitivities for recording ballistic and diffusive photons from different regions of the outer retina.

Location of Parapapillary Gamma Zone and Vertical Fovea Location. The Beijing Eye Study 2011.

Purpose: To assess the spatial relationship between the locations of the parapapillary gamma zone and the fovea. Methods: In a non-glaucomatous subgroup of the population-based Beijing Eye Study population, we measured the mean angle between the optic disc-fovea line and the horizontal (disc-fovea angle), the vertical distance of the fovea from the horizontal through the optic disc center (fovea vertical distance), and the location and width of the widest part of parapapillary gamma zone. Results: The study included 203 individuals (203 eyes; mean axial length, 24.4 ± 1.5 mm; range, 22.03-28.87 mm). The widest gamma zone part was located most often temporal horizontally (51.7%), then inferiorly (43.8%), superiorly (2.5%), and nasally (2.0%). The disc-fovea angle (mean, 7.50° ± 4.00°; range, -6.30° to -23.25°) was significantly higher (P = 0.003; i.e., fovea located more inferiorly) in eyes with the widest gamma zone inferiorly (8.46° ± 4.37°) than in eyes with the widest gamma zone temporally (6.71° ± 3.46°) and in eyes with the widest gamma zone temporally, superiorly, or nasally combined (6.75° ± 3.53°; P = 0.003). The fovea vertical distance (mean, 0.65 ± 0.33 mm; range, -0.20 to 1.67 mm) was longer (P = 0.001; i.e., fovea located more inferiorly) in eyes with the widest gamma zone inferiorly (0.73 ± 0.33 mm) than in eyes with the widest gamma zone temporally (0.58 ± 0.30 mm) and in eyes with a temporal, superior, or nasal gamma zone combined (0.58 ± 0.31 mm; P = 0.001). The fovea vertical distance increased (multivariate analysis) with the widest gamma zone location inferiorly (ß = 0.25; P = 0.001) and wider width of the gamma zone (ß = 0.19; P = 0.01). Conclusions: An inferior fovea location is associated with a wider inferior gamma zone and vice versa, supporting the notion of an inferior shifting of Bruch's membrane as the cause for an inferior gamma zone.

Assessing Interocular Symmetry of the Foveal Cone Mosaic.

Purpose: To test the hypothesis that foveal cone topography is symmetrical between contralateral eyes. Methods: We used adaptive optics scanning light ophthalmoscopy to acquire images of the foveal cone mosaic in each eye of 58 subjects with normal vision (35 female, 23 male). Cones were semiautomatically identified over a 300 × 300-µm foveal area. From these cone coordinates, maps of cone density were derived, and we extracted estimates of peak cone density from each map. Mosaic regularity was assessed using Voronoi cell area regularity (VCAR). Average roundness and average area of the 70%, 75%, 80%, 85%, and 90% of peak density isodensity contours were evaluated. Results: The average peak cone density for right eyes was 180,286 cones/mm2 (n = 49) and for left eyes was 182,397 cones/mm2 (n = 45), with a mean absolute difference of 6363 cones/mm2 (n = 43). Peak density, cone spacing, VCAR, and average area within the isodensity contours of fellow eyes were not significantly different (P = 0.60, P = 0.83, P = 0.30, and P = 0.39, respectively). However, the average roundness of the isodensity contours was 2% more circular in the right eyes than in the left eyes (P = 0.02). Conclusions: There is interocular symmetry of peak foveal cone density, mosaic regularity, and area encompassing the most densely packed cells in subjects with normal vision. The origin and significance of the observed interocular difference in average roundness of the isodensity contours are unclear.

In vivo assessment of foveal geometry and cone photoreceptor density and spacing in children.

The fovea undergoes significant developmental changes from birth into adolescence. However, there is limited data examining cone photoreceptor density, foveal pit shape, and foveal avascular zone (FAZ) size in children. The purpose of this study was to determine whether overall foveal structure differs as a function of age and refractive status in children. Forty-eight healthy children (ages 5.8 to 15.8 years) underwent optical coherence tomography imaging to quantify foveal point thickness and foveal pit diameter, depth, and slope. Adaptive optics scanning laser ophthalmoscope (AOSLO) images of foveal capillaries and cone photoreceptors were acquired in a subset of children to quantify FAZ metrics and cone densities at 0.2, 0.3, and 0.5 mm eccentricities. Results show that foveal pit and FAZ metrics were not related to age, axial length, or refractive status. However, linear cone density was lower in myopic versus non-myopic children at eccentricities of 0.2 mm (mean ± SD = 50,022 ± 5,878 cones/mm2 vs 58,989 ± 4,822 cones/mm2, P < 0.001) and 0.3 mm (43,944 ± 5,547 cones/mm2 vs 48,622 ± 3,538 cones/mm2, P < 0.001). These results suggest FAZ and foveal pit metrics do not systematically differ with age in children, while myopic eyes have decreased linear cone density near the foveal center. Significance Statement: The development of the fovea begins prior to birth and continues through the early teenage years until it reaches adult-like properties. Although the majority of changes during childhood are related to the maturation and migration of cone photoreceptors, in vivo data describing cone packing in children is limited. We assessed overall foveal structure in children as young as 5.8 years old by quantifying cone density and spacing, foveal avascular zone size, and foveal pit morphometry to investigate potential structural differences as a function of age and refractive status. While foveal avascular zone and foveal pit metrics did not significantly differ with age, results indicate that myopic children have lower linear cone densities close to the foveal center compared to non-myopic children.

Inter-individual differences in foveal shape in a scavenging raptor, the black kite Milvus migrans.

Birds, and especially raptors, are believed to forage mainly using visual cues. Indeed, raptors (scavengers and predators) have the highest visual acuity known to date. However, scavengers and predators differ in their visual systems such as in their foveal configuration. While the function of the foveal shape remains unknown, individual variation has never been quantified in birds. In this study, we examined whether foveal shape differs among individuals in relation to eye size, sex, age, eye (left or right) and genetic proximity in a scavenging raptor, the black kite Milvus migrans. We assessed foveal shape in 47 individuals using spectral domain optical coherence tomography (OCT) and geometric morphometric analysis. We found that foveal depth was significantly related to eye size. While foveal width also increased with eye size, it was strongly related to age; younger individuals had a wider fovea with a more pronounced rim. We found no relationship between foveal shape and genetic proximity, suggesting that foveal shape is not a hereditary trait. Our study revealed that the shape of the fovea is directly linked to eye size and that the physical structure of the fovea may develop during the entire life of black kites.

FOVEAL SPARING INTERNAL LIMITING MEMBRANE PEELING FOR IDIOPATHIC MACULAR HOLES: EFFECTS ON ANATOMICAL RESTORATION OF THE FOVEA AND VISUAL FUNCTION.

PURPOSE: Muller cells seem to be important in maintaining foveal morphology through connections between their foot processes and the internal limiting membrane (ILM). Internal limiting membrane peeling causes Muller cell trauma. We hypothesized that leaving a rim of unpeeled ILM around idiopathic macular holes undergoing vitrectomy surgery would improve postoperative foveal morphology and vision. METHODS: Prospective pilot study of fovea-sparing ILM peeling in a consecutive cohort of patients with macular holes over a 12-month period. Spectral-domain optical coherence tomography and Early Treatment Diabetic Retinopathy Study letters best-corrected visual acuity were assessed preoperatively and postoperatively, and foveal morphology and metamorphopsia postoperatively. The foveal sparing group was compared with a second consecutive cohort who received standard ILM peeling (control group). RESULTS: Thirty-four eyes of 34 patients were included in each group. Groups showed no significant preoperative differences. 34/34 holes were successfully closed with surgery in the foveal sparing group and 32/34 in the control group. The foveal sparing group showed better postoperative best-corrected visual acuity (67.7 vs. 63.8, P = 0.003) and best-corrected visual acuity improvement (25.1 vs. 20.2, P = 0.03). The foveal sparing group demonstrated thicker minimum foveal thickness (211 vs. 173 µm, P = 0.002) and less steep foveal depression (158 vs. 149, P = 0.002). CONCLUSION: Preserving nonpeeled ILM around macular holes resulted in a high closure rate, improved foveal morphology, and better postoperative best-corrected visual acuity. An appropriately powered randomized controlled study is warranted.

Subfoveal choroidal thickness at age 9 years in relation to clinical and perinatal characteristics in the population-based Generation R Study.

PURPOSE: To assess the association between clinical and perinatal characteristics and subfoveal choroidal thickness in 9-year-old children. METHODS: The study included data from the population-based Generation R cohort, whose participants underwent cycloplegic refractometry, ocular biometry, height, weight and subfoveal choroidal thickness measurements using a swept-source optical coherence tomography (SS-OCT) instrument. Birth parameters were obtained using medical records. Statistical analyses were performed using multivariate regression models adjusted for age, ethnicity and sex. RESULTS: A total of 1018 children (52.5% girls, 47.5% boys) with a mean age of 9.9 ± 0.3 years and a mean cycloplegic spherical equivalent refraction of 0.80 ± 1.1 D in boys and 0.81 ± 1.4 in girls were eligible for analysis. The subfoveal choroid was 17 µm thicker in girls (298 ± 60.6 µm) than in boys (281 ± 55.0 µm; p < 0.001), a difference of 9.1 µm persisting after adjustment for age, ethnicity and axial length (p = 0.017). Subfoveal choroidal thickness decreased with increasing ocular axial length (-16.2 µm/mm, 95% CI -21.2 to -12.4, p < 0.001) and with increasing myopic refraction (-10.0 µm/D, 95% CI 6.8-13.1; p < 0.001, adjusted for age, ethnicity, axial length and sex) while it increased with increasing body height (1.3 µm/cm, 95% CI 0.8 to 1.9, p < 0.001). Additionally, choroidal thickness increased with increasing birthweight (13.0 µm/kg; 95% CI 0.006-0.020; p < 0.001) and increasing size for gestational age (8.2 µm/kg; 95% CI 4.6-11.8; p < 0.001). Smoking up until the time that pregnancy became known was associated with a thinner choroid (p = 0.016). There was no detectable effect of alcohol consumption. The distributions of axial length, refraction and choroidal thickness were narrower than in older populations. CONCLUSION: The subfoveal choroid was thicker in girls than in boys, and higher body height, higher birthweight and larger size for gestational age were associated with a thicker subfoveal choroid. The implications of these findings for myopia development need further evaluation in longitudinal studies.

Normative database and determinants of macular vessel density measured by optical coherence tomography angiography.

IMPORTANCE: To provide a normative vessel density (VD) database for the macula through swept-source optical coherence tomography angiography (OCTA) and to assess the main determinants of this measurement. BACKGROUND: In contrast with dye angiography, the recently introduced OCTA technique allows for the non-invasive measurement of retinal and choroidal VD metrics. DESIGN: Cross-sectional study. PARTICIPANTS: The right eyes of 346 healthy subjects were studied. In 105 subjects both eyes were imaged. METHODS: Foveal and parafoveal macular VD measurements were obtained in the retinal superficial capillary plexus (SCP), deep capillary plexus (DCP), and in the choriocapillaris (CC) layer. Also recorded were age, sex, axial length (AL), foveal and choroidal thickness (CT). MAIN OUTCOME MEASURES: Normative database and determinants of macular VD measured by OCTA. RESULTS: Mean participant age was 38.3 ± 20.1 years (mean ± SD) (range 5-83). Foveal VDs in the different plexuses were: SCP 22.1% ± 5.0% (7.3-35.1), DCP 19.9% ± 6.3% (6.9-51.2) and CC: 52.8% ± 4.3% (40.2-62.1). Parafoveal VDs ranged from 45.4% ± 3.7% to 51.8% ± 4.6%. Positive correlation was observed between foveal VD and foveal thickness (R = .327), as well as between parafoveal DCP VD and CT (R = .250;P ≤ .006), while correlation with age was negative in the SCP and CC (R = -.283;P < .001). No associations were detected between macular VD and sex or AL (P ≥ .05). CONCLUSION AND RELEVANCE: Macular VD showed wide individual variation, was positively correlated with foveal thickness and with CT, negatively correlated with age, and showed no correlation with AL or sex.

Disc-foveal angle and ocular counterrolling as a key in its interpretation. / El ángulo papila-fóvea y la torsión ocular compensatoria, clave en su interpretación.

PURPOSE: Describe a time-sparing technique to measure disc-foveal angle (DFA), determine normal values and its role when analyzing paired fundus photographs. METHODS: DFA was analysed using the software program Keynote v.6.2.2 on 440 fundus photographs (3D OCT 2000, Topcon Corporation, Tokio, Japan) of 20 individuals. The 11 different head positions were determined with the cervical range of motion device (CROM, Performance Attainment Associates). A reproducibility and correlation study between two fundus cameras (OCT 3D-2000 and TRC-50EX, Topcon Corporation, Tokio, Japan) was performed. RESULTS: Mean DFA of the right and left eye was 5.5±3.4° and 8.6±2.9°, with a difference of 3.1° (P=0.001 Wilcoxon signed-rank test) in the upright head position. Mean absolute difference in DFA between eyes was 3.5±2.6°; an increase was seen with increasing head tilt (P=0.000 Wilcoxon signed-rank test). Mean sum of DFA in both eyes was 14.1±5.4°. On head-tilt of 20° and 40° to the right, mean ocular counterrolling (OCR) was 7.1° and 12.2° in the right eye and 7.7° and 12.1° in the left eye. On head-tilt of 20° and 40° to the left, OCR was 4.4° and 8° in the right eye and 4.2° and 8.7° in the left eye (P=0.000 Wilcoxon signed-rank test). The two cameras showed strong correlation and high reproducibility. CONCLUSIONS: Our DFA measurement technique is time-sparing and reproducible. Left eye shows higher DFA than right eye. OCR occurs only in the roll plane. This information is of value when analyzing paired fundus photographs.

Analysis of Hyperreflective Dots Within the Central Fovea in Healthy Eyes Using En Face Optical Coherence Tomography.

Purpose: The purpose of this retrospective study was to describe and quantify superficial hyperreflective dots within the central fovea and correlate them with age, using en face and cross-sectional B-scan optical coherence tomography (OCT). Methods: Healthy eyes, evaluated with a spectral domain instrument (primary cohort) at the Stein Eye Institute (UCLA) and with a swept source instrument (secondary cohort) at the Vitreous Retina Macula Consultants of New York, were included in this study. En face OCT images (3 × 3 mm) segmented at the level of the superior vascular plexus were acquired, and hyperreflective dots in the foveal avascular zone were quantified by two different methodologies. The threshold reflectivity methodology quantified these dots on a cropped en face OCT image using ellipsoid zone mean reflectivity as the threshold cutoff. The OCT B-scan methodology consisted of a manual count of elevated hyperreflective signals on B-scans that colocalized with the dots by en face OCT. Primary outcome was to quantify these dots and correlate them with age. Results: A total of 44 healthy eyes were evaluated in the primary cohort, and 16 healthy eyes were evaluated in the secondary cohort. The hyperreflective dots steadily increased in number, especially in patients older than 50 years of age, with a strongly positive statistical significant correlation, using both quantitative strategies. Conclusions: Remarkable superficial hyperreflective dots in the central fovea of healthy subjects are novel anatomical findings that may be readily identified with both en face and cross-sectional OCT and steadily increase in number with age. We propose that these dots may represent a normal anatomical landmark, such as Müller cell end feet or inner limiting membrane basal lamina.

Human foveal cone photoreceptor topography and its dependence on eye length.

We provide the first measures of foveal cone density as a function of axial length in living eyes and discuss the physical and visual implications of our findings. We used a new generation Adaptive Optics Scanning Laser Ophthalmoscope to image cones at and near the fovea in 28 eyes of 16 subjects. Cone density and other metrics were computed in units of visual angle and linear retinal units. The foveal cone mosaic in longer eyes is expanded at the fovea, but not in proportion to eye length. Despite retinal stretching (decrease in cones/mm2), myopes generally have a higher angular sampling density (increase in cones/deg2) in and around the fovea compared to emmetropes, offering the potential for better visual acuity. Reports of deficits in best-corrected foveal vision in myopes compared to emmetropes cannot be explained by increased spacing between photoreceptors caused by retinal stretching during myopic progression.

Circularity of the foveal avascular zone and its correlation with parafoveal vessel density, in subjects with and without diabetes.

PURPOSE: To characterize the distribution of the foveal avascular zone circularity and its correlation with parafoveal vessel density, in subjects with and without diabetes. METHODS: Observational, descriptive, cross-sectional, and prospective study; subjects without diabetes (Group 1), with diabetes without retinopathy (Group 2), or with diabetic retinopathy (Group 3) were included. Means of foveal avascular zone circularity and parafoveal vessel density were compared between groups (Kruskal-Wallis) and their correlation was calculated with Spearman's Rho test. RESULTS: Seventy-seven eyes; central vessel density mean was higher in Group 1 than in Group 2 and higher in Group 2 than in Group 3; inner and complete vessel density means were also higher in Group 2 than in Group 3. The mean of the foveal avascular zone circularity did not differ between groups, and in Group 3 it had a positive correlation with central (0.45), inner (0.56), and complete (0.53) vessel densities. CONCLUSIONS: Circularity does not differ between subjects with diabetes, with and without retinopathy, and has only a low correlation with parafoveal vessel density in people with diabetic retinopathy, which does not allow anticipating a reduction of vessel density in this disease.

OBJETIVO: Caracterizar la distribución de la circularidad de la zona avascular foveal y su correlación con la densidad vascular perifoveal, en sujetos con y sin diabetes. MÉTODO: Estudio observacional, descriptivo, transversal y prospectivo; se incluyeron sujetos sin diabetes (Grupo 1), con diabetes sin retinopatía (Grupo 2) y con retinopatía diabética (Grupo 3). Los promedios de circularidad de la zona avascular foveal y de la densidad vascular parafoveal se compararon entre grupos (Kruskal-Wallis), y se calculó su correlación mediante la prueba Rho de Spearman. RESULTADOS: Se estudiaron 77 ojos. El promedio de la densidad vascular central fue mayor en el Grupo 1 que en el Grupo 2, y mayor en el Grupo 2 que en el Grupo 3. Los promedios de la densidad vascular interna y completa también fueron mayores en el Grupo 2 que en el Grupo 3. El promedio de la circularidad de la zona avascular foveal no difirió entre grupos, y en el Grupo 3 tuvo una correlación positiva con la densidad vascular central (0.45), interna (0.56) y completa (0.53). CONCLUSIONES: La circularidad no difiere entre sujetos con y sin diabetes, con y sin retinopatía, y solo tiene una baja correlación con la densidad vascular parafoveal en sujetos con retinopatía diabética, lo cual no permite anticipar una reducción de la densidad vascular en esta enfermedad.

Foveal and parafoveal choroidal thickness pattern measuring by swept source optical coherence tomography.

OBJECTIVE: To evaluate the choroidal thickness (CT) in foveal and parafoveal regions in Thai adults using swept-source optical coherence tomography (SS-OCT). METHODS: We enrolled healthy volunteers ≥18 years of age from King Chulalongkorn Memorial Hospital, Thailand, during September 2015 to March 2016. Optical coherence tomography (OCT) of the macula was performed, and subfoveal CT was measured manually using a line scan. Average thicknesses of retinal and choroidal layers in regions of the Early Treatment Diabetic Retinopathy Study grid were measured automatically. A multivariate analysis was conducted to determine correlations between CTs in the foveal and parafoveal regions and retinal layers. RESULTS: Altogether, 144 eyes from 144 subjects (29 men, 115 women; mean age 41 years) were studied. The mean foveal CT was 282.4 ± 13.8 µm. It was thicker in the temporal fovea than in the nasal fovea (p < 0.001) and thicker in men than in women. Multivariate analysis showed that age and sex were significantly negatively correlated with the thickness of the retina, ganglion cell layer, outer retinal layer, and choroid but not of the nerve fiber layer. Regression analysis revealed that the CT decreased approximately 1.5 µm per year. CONCLUSIONS: Age and sex significantly influence choroidal thickness. Macular CT in a healthy eye thins with age. CT decreases with age faster at distances away from the foveal center than at the center. Subfoveal CT was greater than the mean CT. Parafoveal CT should be evaluated to identify specific retinal-choroidal disease.

Structure and function of the bird fovea.

The cellular structure and functional relevance of the bird fovea are still incompletely understood. This review gives an overview of the cellular composition of the bird fovea, with special regard to Müller glial cells that provide the mechanical stability of the foveal tissue. A survey of previous data shows that the visual acuity of different bird groups (with the exception of owls) depends on the eye size, while the shape of the foveal pit does not correlate with the visual acuity. Among various bird groups, the foveal pit may have two depths, shallow (80-120 µm) or deep (190-240 µm). There is a long-lasting debate whether the bird fovea acts as a local image enlarger or as a focus indicator and movement detector. These functions are supported by the refraction of the incoming light at the tissue surface. However, it was shown that Müller cells form highly refractive layers in the centre and walls of the deep avian fovea (Nature, 1978, 275, 127). Analysis of the light path through the tissue may suggest that Müller cell layers serve at least two optical functions: magnification of the image in the foveal centre and light focusing into a point within and/or a ring around the foveal centre. It is suggested that Müller glial cells contribute to various optical functions of the bird fovea.

Simulating an Anti-Vascular Endothelial Growth Factor Switch in Neovascular Age-Related Macular Degeneration: A HARBOR Subanalysis.

PURPOSE: A simulated switching study assessed the effects of continuing the same anti-vascular endothelial growth factor (VEGF) treatment among patients who typically are considered for a therapy switch. Post hoc analysis of data from HARBOR was undertaken. Patients with neovascular age-related macular degeneration who demonstrated a suboptimal response after 3 or 6 months of ranibizumab treatment were identified as switching candidates. Rather than switching, however, patients continued on ranibizumab treatment, and visual and anatomic outcomes from the point of the hypothetical switch were examined. DESIGN: Post hoc analysis of the phase 3 HARBOR clinical trial. PARTICIPANTS: Patients were included in 3- and 6-month switcher analyses if they received 3 of 3 initial monthly ranibizumab doses and 5 of 6 initial monthly ranibizumab doses, respectively, and met all the following: 5-letter or fewer gain from baseline, best-corrected visual acuity (BCVA) 20/40 or worse, and intraretinal or subretinal fluid with central foveal thickness (CFT) equal to or greater than central subfield thickness. METHODS: Patient data were examined at months 3 and 6 to identify those who met predetermined switching criteria. Best-corrected visual acuity and CFT were examined from the point at which switching criteria were met through months 6, 12, 18, and 24 of HARBOR and compared with those who did not meet the criteria. MAIN OUTCOME MEASURES: Outcome measures included mean BCVA and CFT change over time from the point (month 3 or 6) at which switching criteria were met. RESULTS: By months 3 and 6, only 44 of 1059 patients (4.2%) and 37 of 769 patients (4.8%), respectively, met the inclusion criteria for hypothetical switching. Patients who met switching criteria at month 3 gained, on average, 5.3 letters from months 3 to 12 and 2.7 letters from months 3 to 24. Month 6 switchers gained, on average, 1.6 letters from months 6 to 12 and 1.8 letters from months 6 to 24. Both groups experienced significant CFT reductions over 24 months. CONCLUSIONS: Month 3 hypothetical switchers achieved vision and anatomic improvement while continuing their original ranibizumab treatment. Month 6 switcher outcomes replicated those commonly reported in published anti-VEGF switching studies: stable vision or nominal improvements in vision with continued substantial anatomic improvement.

The Fovea-BMO Axis Angle and Macular Thickness Vertical Asymmetry Across The Temporal Raphe.

PURPOSE: To test the hypothesis that the fovea-Bruch's membrane opening (FoBMO) axis angle influences the thickness symmetry of the macular ganglion cell/inner plexiform layer (GCIPL) across the temporal horizontal meridian in normal subjects. DESIGN: Cross-sectional diagnostic study at a tertiary academic center. METHODS: One hundred sixteen eyes of 60 normal subjects aged 40 to 85 years underwent spectral domain optical coherence tomography(SD-OCT) imaging. The FoBMO angle was estimated on en face infrared SD-OCT images. Posterior Pole algorithm images acquired with Spectralis SD-OCT were used to define vertical asymmetry as follows. The average thickness difference between the 3 most temporal superpixels above and below the horizontal meridian, the second row of superpixels from the horizontal meridian, and 3 central superpixels above and below the horizontal meridian were calculated. Factors influencing GCIPL thickness asymmetry were explored and changes in thickness asymmetry as a function of FoBMO angle were investigated. RESULTS: No demographic or clinical factors affected temporal GCIPL asymmetry (P>0.05 for all). A more (negatively) tilted FoBMO angle was associated with relatively thinner inferior compared with superior GCIPL thickness in superpixels immediately adjacent to the temporal raphe (P<0.001). The second row of temporal superpixels from the horizontal meridian (P=0.349) or central superpixels (P=0.292) did not show this tendency. CONCLUSIONS: Vertical GCIPL symmetry across the horizontal meridian is influenced by the FoBMO angle. SD-OCT algorithms using vertical asymmetry as a diagnostic index should be adjusted for the FoBMO angle.

Normative Data on Foveal Avascular Zone Dimensions in Four Macular Vascular Layers.

BACKGROUND AND OBJECTIVES: To provide normative data on the size of the foveal avascular zone (FAZ) in the four histological retinal vascular layers as measured using optical coherence tomography angiography (OCTA) and evaluate interobserver variability. PATIENTS AND METHODS: Two graders measured the FAZ area in each layer (nerve fiber layer [NFL], ganglion cell layer [GCL], inner plexiform layer to inner nuclear layer [INL], and INL to outer plexiform layer), as well as the superficial and deep capillary plexuses. RESULTS: Forty-seven eyes of 25 subjects were included. The FAZ was not clearly delineated in the NFL or GCL layers. There was high agreement between measurements of the FAZ area of the different layers. Inter- and intraobserver agreements were high. CONCLUSION: This is the first study to measure FAZ size across the retina. There was a high correlation between FAZ sizes among the different layers on OCTA. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:580-586.].

The primate fovea: Structure, function and development.

A fovea is a pitted invagination in the inner retinal tissue (fovea interna) that overlies an area of photoreceptors specialized for high acuity vision (fovea externa). Although the shape of the vertebrate fovea varies considerably among the species, there are two basic types. The retina of many predatory fish, reptilians, and birds possess one (or two) convexiclivate fovea(s), while the retina of higher primates contains a concaviclivate fovea. By refraction of the incoming light, the convexiclivate fovea may function as image enlarger, focus indicator, and movement detector. By centrifugal displacement of the inner retinal layers, which increases the transparency of the central foveal tissue (the foveola), the primate fovea interna improves the quality of the image received by the central photoreceptors. In this review, we summarize ‒ with the focus on Müller cells of the human and macaque fovea ‒ data regarding the structure of the primate fovea, discuss various aspects of the optical function of the fovea, and propose a model of foveal development. The "Müller cell cone" of the foveola comprises specialized Müller cells which do not support neuronal activity but may serve optical and structural functions. In addition to the "Müller cell cone", structural stabilization of the foveal morphology may be provided by the 'z-shaped' Müller cells of the fovea walls, via exerting tractional forces onto Henle fibers. The spatial distribution of glial fibrillary acidic protein may suggest that the foveola and the Henle fiber layer are subjects to mechanical stress. During development, the foveal pit is proposed to be formed by a vertical contraction of the centralmost Müller cells. After widening of the foveal pit likely mediated by retracting astrocytes, Henle fibers are formed by horizontal contraction of Müller cell processes in the outer plexiform layer and the centripetal displacement of photoreceptors. A better understanding of the molecular, cellular, and mechanical factors involved in the developmental morphogenesis and the structural stabilization of the fovea may help to explain the (patho-) genesis of foveal hypoplasia and macular holes.