Association of drusen deposition with choroidal intercapillary pillars in the aging human eye

PURPOSE. To determine the pattern of drusen accumulation with age and to investigate the initial sites of deposition and their relationship to choroidal capillaries in human donor eyes from the eye bank of Moorfields Eye Hospital.METHODS. Wholemounted, hydrated preparations of the choriocapillaris and Bruch's membrane from donor eyes ranging from 42 to 95 years, with or without retinal pigment epithelium (RPE), were examined by conventional and confocal microscopy. Drusen were visualized by their autofluorescence.RESULTS. In all age groups studied autofluorescent drusen were present at the equator but were not found centrally where the vascular architecture is different, being tubular rather than a honeycomb pattern. Autofluorescing drusen were strongly associated with the lateral walls of the choriocapillaris (an area commonly known as the intercapillary pillars of the choriocapillaris (P = 0.028; Wilcoxon signed ranks test). Nonfluorescing drusen were occasionally seen centrally, but were not easily identified, and because of their large size, their localization with respect to capillary walls was not possible.CONCLUSIONS. These results strongly support the notion that autofluorescent drusen are not randomly distributed and have a specific spatial relationship to choroidal vessel walls. That equatorial drusen fluoresce, whereas central drusen do not, suggests that they may have different chemical compositions at the two sites and possibly different significance in age-related macular disease

Optical coherence tomography angiography of foveal hypoplasia

AIMS: To discuss foveal development in the context of detailed retinal vasculature imaging in foveal hypoplasia using optical coherence tomography angiography. METHODS: In this case series, the optical coherence tomography angiography results of four patients with idiopathic foveal hypoplasia and two patients with foveal hypoplasia secondary to oculocutaneous albinism are presented. RESULTS: Cases with intact visual acuity demonstrated lower grades of foveal hypoplasia on optical coherence tomography, while those with poor vision demonstrated high grades of foveal hypoplasia. The superficial retinal capillary plexus was intact in the foveal area in all cases, with no demonstrable foveal avascular zone. The deep retinal capillary plexus was absent to variable degrees in most cases, but was most persistent in those cases with reduced vision. CONCLUSIONS: The superficial retinal capillary plexus is present in cases with foveal hypoplasia, while the deep retinal capillary plexus is absent to varying degrees. Our findings support the hypothesis that an intact foveal avascular zone of the deep capillary plexus allows for outer retinal photoreceptor specialisation to occur unimpeded, resulting in preserved visual acuity, while this process may be inhibited by an absent deep capillary foveal avascular zone with resultant poor vision

State of the art spatial visualization of the response of neovascularisation to anti-vascular endothelial growth factor therapy

PURPOSE: To visualize the mode of action of anti-vascular endothelial growth factor (anti-VEGFs) therapy on retinal neovascularization (RNV) in a patient with macular telangiectasia (MacTel) type 2 using a detailed three-dimensional data environment. OBSERVATION: A 60-year-old man presented with visual acuity loss and was diagnosed with MacTel type 2. Fluorescein angiography was not possible for safety reasons because of a history of severe reaction to fluorescein dye at his referring hospital. Optical coherence tomography angiography (OCTA) imaging revealed new retinal neovascular membranes (RNV) in the macula of both eyes. A marked reduction in the size of the RNV in both eyes was evident on volume-rendered three-dimensional OCTA retinal imaging after the first anti-VEGF injection. CONCLUSION AND IMPORTANCE: The ability to directly observe the effect of anti-VEGF injections on a RNV using three-dimensional OCTA was successfully demonstrated. This can be useful in patients with previous allergic and potentially lethal complications to fluorescein. In addition, enhanced three-dimensional spatial display of RNV leads to a greater understanding of the perfusion profile and the anatomical changes that occur in ocular neovascularization relative to surrounding tissue. This has the potential to provide insight into the pathobiology of angiogenesis

Progression of Retinopathy Secondary to Maternally Inherited Diabetes and Deafness – Evaluation of Predicting Parameters

PURPOSE: To investigate the prognostic value of demographic, functional, and imaging parameters on retinal pigment epithelium (RPE) atrophy progression secondary to Maternally Inherited Diabetes and Deafness (MIDD) and to evaluate the application of these factors in clinical trial design. DESIGN: Retrospective observational case series. METHODS: Thirty-five eyes of 20 patients (age range, 24.9-75.9 years) with genetically proven MIDD and demarcated RPE atrophy on serial fundus autofluorescence (AF) images were included. Lesion size and shape-descriptive parameters were longitudinally determined by two independent readers. A linear mixed effect model was used to predict the lesion enlargement rate based on baseline variables. Sample size calculations were performed to model the power in a simulated interventional study. RESULTS: The mean follow-up time was 4.27 years. The mean progression rate of RPE atrophy was 2.33 mm2/year revealing a dependence on baseline lesion size (+0.04 [0.02-0.07] mm2/year/mm2, p<0.001), which was absent after square root transformation. The fovea was preserved in the majority of patients during the observation time. In the case of foveal involvement, the loss of visual acuity lagged behind central RPE atrophy in AF images. Sex, age, and number of atrophic foci predicted future progression rates with a cross-validated mean absolute error of 0.13 mm/year and to reduce the required sample size for simulated interventional trials. CONCLUSIONS: Progressive RPE atrophy could be traced in all eyes using AF imaging. Shape-descriptive factors and patients' baseline characteristics had significant prognostic value, guiding appropriate subject selection and sample size in future interventional trial design

Foveal structure and visual function in nanophthalmos and posterior microphthalmos

Background/aims: The reason for visual impairment in patients with nanophthalmos and posterior microphthalmos is not completely understood. Therefore, this study aims to investigate foveal structure, and the impact of demographic, clinical and imaging parameters on best-corrected visual acuity (BCVA) in these conditions. Methods: Sixty-two eyes of 33 patients with nanophthalmos (n=40) or posterior microphthalmos (n=22), and 114 eyes of healthy controls with high-resolution retinal imaging including spectral-domain or swept-source optical coherence tomography images were included in this cross-sectional case-control study. Foveal retinal layer thickness was determined by two independent readers. A mixed-effect model was used to perform structure-function correlations and predict the BCVA based on subject-specific variables. Results: Most patients (28/33) had altered foveal structure associated with loss of foveal avascular zone and impaired BCVA. However, widening of outer nuclear layer, lengthening of photoreceptor outer segments, normal distribution of macular pigment and presence of Henle fibres were consistently found. Apart from the presence of choroidal effusion, which had significant impact on BCVA, the features age, refractive error, axial length and retinal layer thickness at the foveal centre explained 61.7% of the variability of BCVA. Conclusion: This study demonstrates that choroidal effusion, age, refractive error, axial length and retinal layer thickness are responsible for the majority of interindividual variability of BCVA as well as the morphological foveal heterogeneity in patients with nanophthalmos or posterior microphthalmos. This might give further insights into the physiology of foveal development and the process of emmetropisation, and support clinicians in the assessment of these disease entities

The effects of macular ischemia on visual acuity in diabetic retinopathy

PURPOSE: To investigate the impact of diabetic macular ischemia (DMI) on visual acuity (VA), through the analysis of novel fluorescein angiography (FA) parameters. METHODS: Data were retrospectively collected over a 6-month period. DMI severity was graded using Early Treatment Diabetic Retinopathy Study (ETDRS) protocols. Custom software was used to quantify areas of the foveal avascular zone (FAZ), and of capillary nonperfusion over the papillo-macular nerve fiber layer bundle, and temporal macula, and associations tested with VA. RESULTS: A total of 488 patients with type 2 diabetes mellitus and FAs of sufficient quality to allow detailed quantitative analyses were included. ETDRS-DMI SEVerity was graded as: none, 39.7%; questionable, 18.4%; mild, 25.2%; moderate, 11.0%; and severe, 5.6%. Median FAZ areas were 0.19 mm(2) (interquartile range [IQR], 0.13-0.25); 0.25 mm(2) (IQR, 0.18-0.32); 0.27 mm(2) (IQR, 0.19-0.38); 0.32 mm(2) (IQR, 0.25-0.54); and 0.78 mm(2) (IQR, 0.60-1.32), respectively, and were significantly different between all grades (P < 0.002), apart from "questionable" versus "mild" grades. Significant association of VA to FAZ area was observed only in the moderate (β = 0.406, SE = 0.101, P = 0.001) and severe (β = 0.299, SE = 0.108, P = 0.006) subgroups, but not in milder ETDRS-DMI grades. A strong association with VA was observed in cases with papillomacular ischemia (β = 1.123, SE = 0.355, P = 0.005), independent of FAZ size or the presence of macular edema. CONCLUSIONS: Diabetic macular ischemia is associated with reduced VA in eyes with moderate to severe ETDRS-DMI grades of ischemia but preserved in milder grades. In addition, we describe the independent association of papillomacular nerve fiber bundle ischemia with reduced VA

The Moorfields AMD Database Report 2 - Fellow Eye Involvement with Neovascular Age-related Macular Degeneration

BACKGROUND/AIMS: Neovascular age-related macular degeneration (nAMD) is frequently bilateral, and previous reports on ‘fellow eyes’’ have assumed sequential treatment after a period of treatment of the first eye only. The aim of our study was to analyse baseline characteristics and visual acuity (VA) outcomes of fellow eye involvement with nAMD, specifically differentiating between sequential and non-sequential (due to macular scarring in the first eye) anti-vascular endothelial growth factor treatment and timelines for fellow eye involvement. METHODS: Retrospective, electronic medical record database study of the Moorfields AMD database of 8174 eyes/120,756 single entries with data extracted between October 21, 2008 and August 9, 2018. The dataset for analysis consisted of 1180 sequential, 413 nonsequential, and 1110 unilateral eyes. RESULTS: Mean VA of sequentially treated fellow eyes at baseline was significantly higher (62±13), VA gain over two years lower (0.65±14), and proportion of eyes with good VA (≥20/40 or 70 letters) higher (46%) than the respective first eyes (baseline VA 54±16, VA gain at two years 5.6±15, percentage of eyes with good VA 38%). Non-sequential fellow eyes showed baseline characteristics and VA outcomes similar to first eyes. Fellow eye involvement rate was 32% at two years, and median time interval to fellow eye involvement was 71 (IQR 27-147) weeks. CONCLUSION: This reports shows sequentially treated nAMD fellow eyes have better baseline and final VA than non-sequentially treated eyes after 2 years of treatment. Sequentially treated eyes also had a greater proportion with good VA after 2 years of treatment. PRECIS Depending on age, fellow eye involvement occurs in 32% of patients with neovascular AMD by two years. Fellow eyes generally maintain better vision, except in cases where late-stage disease in the first eye was untreated

Evaluation of Nonperfused Retinal Vessels in Ischemic Retinopathy

Purpose: Retinal ischemia has been traditionally assessed by fluorescein angiography, visualizing perfused vessels. However, this method does not provide any information about nonperfused vessels, and although it is often assumed that vessels in ischemic areas regress, we know little about how nonperfused retinal vessels change over time. Here, we aim to learn more about the long-term fate of nonperfused vessels in the retinal vasculature. Methods: Optical coherence tomography (OCT) was used to visualize perfusion as well as structural properties of the retinal vasculature in patients suffering from retinal vascular occlusions. In addition, postmortem tissue from a patient with long standing (6 years) central retinal vein occlusion (CRVO) was investigated, using immunohistochemistry on whole-mount retina and paraffin sections to visualize blood vessel components. Results: Comparing OCT angiography with enface OCT images revealed that in ischemic areas of the retina, nonperfused, larger vessels could be detected as hyperreflective structures in enface OCT images. Furthermore, analysis of a postmortem tissue sample from a CRVO patient with a large nonperfused region in the macula, revealed preservation of the basement membrane from all retinal vessels, including nonperfused, acellular vessels of all calibers. Conclusions: Our data suggests long-term preservation of vascular basement membrane in ischemic retina. This has implications for therapeutic approaches aiming to alleviate retinal ischemia via the regeneration of damaged vessels