Temporal-to-Nasal Macular Ganglion Cell and Inner Plexiform Layer Ratios in a Large Adult Twin Cohort: Correlations With Age and Heritability.

Purpose: Temporal-to-nasal macular ganglion cell layer thickness ratios are reduced in albinism. We explored similar ratios in a large twin cohort to investigate ranges in healthy adults, correlations with age, and heritability. Methods: More than 1000 twin pairs from TwinsUK underwent macular optical coherence tomography (OCT) scans. Automated segmentation yielded thicknesses for the combined ganglion cell and inner plexiform layer (GCIPL) in Early Treatment of Diabetic Retinopathy Study subfields. Participants with diseases likely to affect these layers or segmentation accuracy were excluded. Inner and outer ratios were defined as the ratio of temporal-to-nasal GCIPL thickness for inner and outer subfields respectively. Corresponding ratios were obtained from a smaller cohort undergoing OCTs with a different device (three-dimensional (3D)-OCT, Topcon, Japan). Results: Scans from 2300 twins (1150 pairs) were included (mean [SD] age, 53.9 (16.5) years). Mean (SD) inner and outer ratios were 0.89 (0.09) and 0.84 (0.11), correlating negatively with age (coefficients, -0.17 and -0.21, respectively). In males (150 pairs) ratios were higher and did not correlate significantly with age. Intrapair correlation coefficients were higher in monozygotic than dizygotic pairs; age-adjusted heritability estimates were 0.20 and 0.23 for inner and outer ratios, respectively. For the second cohort (n = 166), mean (SD) ratios were 0.93 (0.08) and 0.91 (0.09), significantly greater than for the larger cohort. Conclusions: Our study gives reference values for temporal-to-nasal macular GCIPL subfield ratios. Weak negative correlations with age emerged. Genetic factors may contribute to ∼20% to 23% of the variance in healthy individuals. The ratios differ according to the OCT platform used.

Impact of injection frequency on 5-year real-world visual acuity outcomes of aflibercept therapy for neovascular age-related macular degeneration.

BACKGROUND: To evaluate the impact of injection frequency on yearly visual outcomes of patients treated with intravitreal aflibercept for neovascular age-related macular degeneration (nAMD) over a period of 5 years in a tertiary ophthalmic centre. DESIGN: Single centre, retrospective cohort study. PARTICIPANTS: Consecutive treatment-naive nAMD patients initiated on aflibercept injections 5 years ago. METHODS: The Moorfields OpenEyes database was searched for consecutive patients who were initiated on intravitreal aflibercept for nAMD in 2013-14 and the visual acuity (VA) in Early Diabetic Retinopathy Study (ETDRS) letters and injection records per year were recorded for a period of 5 years. Analyses of the whole cohort and a sub-sample of 5-year completers were done. The cohort was further grouped into Group A (on continuous treatment), Group B (early cessation of treatment) and Group C (interrupted treatment) to evaluate the relation between treatment frequency and visual outcomes. MAIN OUTCOME MEASURES: The primary end point was change in VA at 5 years; secondary outcomes included proportion of eyes that gained or maintained VA, number of injections received and the effect of treatment frequency. RESULTS: Data were collected on 468 patients (512 eyes). Sixty-six percent of the patients completed 5-year follow-up. The mean age of the whole cohort was 79.5 ± 8.5 years and the mean baseline VA was 58.3 ± 15.4 letters. Amongst the completers, final VA change was -2.9 (SD 23.4) ETDRS letters and the cumulative number of injections over 5 years was 24.2 (10.6). Group A had three letter gain and received significantly higher cumulative number of injections over 5 years than Group B and C (31.8, 14.6 and 18.4 respectively, p = 0.001). After adjusting for age and baseline VA, on average, final VA was +8.0 letters higher in the ≥20 injections group than the <20 group (p = 0.001). CONCLUSIONS: Aflibercept therapy results in sustained good visual outcome over 5 years in neovascular AMD eyes when early and persistent treatment is given.

Multimodal Imaging in the Management of Choroidal Neovascularization Secondary to Central Serous Chorioretinopathy.

The diagnosis and treatment of choroidal neovascularization (CNV) in eyes with chronic central serous chorioretinopathy (CSCR) can be challenging. The purpose of this study was to classify eyes with suspected CNV using multimodal imaging. The effect of intravitreal anti-vascular endothelial growth factor (VEGF) was assessed and compared to controls. This retrospective study included chronic CSCR patients with suspected secondary CNV who received intravitreal bevacizumab. Eyes were divided into "definite CNV" and "no CNV" based on optical coherence tomography angiography (OCTA). Eyes that did not undergo OCTA imaging were considered as "presumed CNV". One-year outcome in visual acuity (VA) and central foveal thickness (CFT) were investigated and compared to non-treated control patients to assess the response to anti-VEGF. Logistic regression analysis was used to explore predictive biomarkers of CNV detection and improvement after anti-VEGF. Ninety-two eyes with chronic CSCR from 88 participants were included in this study. Sixty-one eyes received bevacizumab and 31 eyes were non-treated control subjects. The presence of subretinal hyperreflective material (SHRM) and shallow irregular retinal pigment epithelium (RPE) elevation (SIRE) with sub-RPE hyperreflectivity on OCT was associated with a significantly increased risk of detecting CNV on OCTA. Intravitreal anti-VEGF caused significant functional and anatomical improvement in patients with neovascular CSCR as compared to non-treated eyes. In contrast, VA and CFT changes were not significantly different between treated and non-treated CSCR with no evidence of CNV on OCTA. No clinical or anatomical biomarkers were found to be associated with response to treatment. In conclusion, OCTA should be used to confirm the presence CNV in suspected chronic CSCR patients. Intravitreal anti-VEGF treatment resulted in a significantly better one-year outcome in patients with definitive OCTA evidence of CNV.

Segmented Macular Layer Volumes from Spectral Domain Optical Coherence Tomography in 184 Adult Twins: Associations With Age and Heritability.

Purpose: To investigate segmented macular layer volumes from a healthy adult twin cohort (TwinsUK), exploring changes with age and heritability. Methods: Macular spectral domain optical coherence tomography images were acquired from monozygotic (MZ) and dizygotic (DZ) twins in a cross-sectional study. The following layer volumes were derived for circles of 3 and 6 mm diameter around the foveal center, using automated segmentation software: retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptors (PR), retinal pigment epithelium (RPE), and total retinal volume (TRV). Correlation coefficients (intereye; age; intrapair for MZ and DZ pairs) were quantified; heritability was estimated using structural equation modeling. Results: Scans from 184 participants were included. Intereye correlation was highest for TRV and GCIPL. Negative correlations with age (for 3- or 6-mm areas, or both) were observed for TRV, RNFL, GCIPL, and INL. Positive correlations were observed for PR, RPE, and OPL. For all layers, intrapair correlation was greater for MZ than DZ pairs. Heritability estimates were highest (>80%) for TRV and GCIPL volume, and lowest for RPE volume. Conclusions: Although TRV was negatively correlated with age, all layers did not show negative correlation. Some inner layers thinned with age, whereas some outer volumes increased (not the ONL). Reduced RPE phagocytic function with age and remodeling in the OPL could be contributing factors. Heritability estimates were highest for inner retinal layers (particularly GCIPL), and lowest for RPE volume.

Association of Longitudinal Changes in Drusen Characteristics and Retinal Layer Volumes with Subsequent Subtype of Choroidal Neovascularisation.

AIM: To investigate the longitudinal correlation between drusen characteristics and retinal layer volumes pre conversion and subsequent type of choroidal neovascularisation (CNV). METHODS: This was a single-centre retrospective study. The study participants were patients with wet age-related macular degeneration (AMD) in one eye who developed wet AMD in the contralateral eye, with at least 2 years of follow-up prior to conversion. The Moorfields Eye Hospital database was searched for eligible patients and their data were recorded. Eyes were classified as occult or classic based on fundus fluorescein angiography. Optical coherence tomography (OCT) images were analysed for drusen characteristics and retinal layer volumes were analysed over time using automated software (Topcon 3D OCT-2000 and Orion, Voxeleron LLC, respectively). All values were obtained at baseline as well as year 1 and year 2 before conversion to wet AMD. RESULTS: Fifty-one eyes with bilateral CNV showed high correlation of type of CNV between eyes (kappa statistic 0.89). A total of 49 wet AMD eyes (29 occult, 20 classic) were analysed for drusen parameters. Two patients with retinal angiomatous proliferation were excluded. Drusen count, area, and volume did not differ by CNV type, but the rates of change of drusen area (p = 0.046) and drusen volume (0.022) were higher in the occult group in the year preceding CNV development. Of the 49 eyes, 17 (10 occult, 7 classic) with available good quality OCT were analysed for retinal layer volumes. There was a progressive reduction in outer nuclear layer (ONL) volume (p = 0.002) and an expansion in outer plexiform layer volume (p = 0.015) in eyes that developed occult CNV. CONCLUSION: Our study shows that rate of increase in drusen load and reduction in ONL are significant features seen in eyes developing occult CNV, highlighting new imaging markers that need to be replicated in larger studies. These markers provide insight into the pathogenesis of CNV and may serve as prognostic indicators, as classic CNV carries a poorer prognosis compared to occult CNV.

Treatment of presumed trematode-induced granulomatous anterior uveitis among children in rural areas of Egypt.

PURPOSE: The purpose of this study is to evaluate the efficacy of systemic antiparasitic medications alone or in combination with surgical aspiration in management of presumed trematode-induced anterior uveitis in children. PATIENTS AND METHODS: Prospective case series. Children who presented with anterior chamber (AC) granuloma were included in the study. All patients received antiparasitic treatment and after 2 weeks; patients were divided based on their clinical improvement in terms of the baseline granuloma area into two groups: group A (<2.5 mm2) who continued on antiparasitic medications only (n = 15) and group B (≥2.5 mm2) who underwent surgical aspiration (n = 15). Basic demographics data, visual acuity (VA), corneal thickness, granuloma area and AC activity (cells and flare) were recorded and analysed. Systemic work-up including stool and urine analysis, full blood count, chest X-ray and schistosomiasis titre were performed. RESULTS: Thirty eyes of 30 patients were included in the study with a mean age of 13.4 ± 2.42 years. All patients were male. Patients were examined and followed at Mansoura Ophthalmic Center, Mansoura University. Both groups showed statistically significant improvement in VA, AC activity, corneal thickness and granuloma area (p-value < 0.001), which was achieved with medical treatment only in group A. However, in group B granuloma required aspiration and did not recur after that. CONCLUSION: Presumed trematode-induced AC granuloma is common among children living in the rural areas of Egypt. Antiparasitic medication alone was found to be effective for small-sized granulomas. Surgical aspiration is an effective adjuvant procedure to treat large-sized ones.

Deep Learning for Prediction of AMD Progression: A Pilot Study.

Purpose: To develop and assess a method for predicting the likelihood of converting from early/intermediate to advanced wet age-related macular degeneration (AMD) using optical coherence tomography (OCT) imaging and methods of deep learning. Methods: Seventy-one eyes of 71 patients with confirmed early/intermediate AMD with contralateral wet AMD were imaged with OCT three times over 2 years (baseline, year 1, year 2). These eyes were divided into two groups: eyes that had not converted to wet AMD (n = 40) at year 2 and those that had (n = 31). Two deep convolutional neural networks (CNN) were evaluated using 5-fold cross validation on the OCT data at baseline to attempt to predict which eyes would convert to advanced AMD at year 2: (1) VGG16, a popular CNN for image recognition was fine-tuned, and (2) a novel, simplified CNN architecture was trained from scratch. Preprocessing was added in the form of a segmentation-based normalization to reduce variance in the data and improve performance. Results: Our new architecture, AMDnet, with preprocessing, achieved an area under the receiver operating characteristic (ROC) curve (AUC) of 0.89 at the B-scan level and 0.91 for volumes. Results for VGG16, an established CNN architecture, with preprocessing were 0.82 for B-scans/0.87 for volumes versus 0.66 for B-scans/0.69 for volumes without preprocessing. Conclusions: A CNN with layer segmentation-based preprocessing shows strong predictive power for the progression of early/intermediate AMD to advanced AMD. Use of the preprocessing was shown to improve performance regardless of the network architecture.

Changes in macular drusen parameters preceding the development of neovascular age-related macular degeneration.

PURPOSE: To assess the rate of change in macular drusen load in fellow eyes of patients with unilateral neovascular age-related macular degeneration (AMD) to evaluate whether the change in drusen load determines the onset and type of choroidal neovascularisation (CNV). METHODS: Subjects with unilateral neovascular AMD with a minimum of 2 years follow-up were identified retrospectively from the hospital electronic database. Drusen count, area and volume measurements at the macula of the contralateral eye were recorded using the commercial software on the Topcon 3D OCT-2000 devices over the previous 2 years. The mean rate of change of these parameters over time was compared between fellow eyes that converted to various CNV subtypes and those that did not. RESULTS: Two hundred forty-eight patients met the inclusion criteria. Of these patients, 179 patients did not progress to neovascular AMD (Group 1) while 69 patients converted (Group 2) at the end of 2 years follow up. Mean drusen volumes and drusen areas increased significantly in Group 2 in the 2nd year by 0.031 mm3 (p < 0.001) and 0.572 mm2 (p = 0.002), respectively. However, there was no difference in the rate of change between the two groups at year 1. Furthermore, for each 0.1 mm increase in the cubed root of baseline mean drusen volume increases the odds of progressing to CNV by 40% (95% CI 1.2-1.6; p < 0.001). The increase in drusen volume was higher in the occult CNV group compared to classic CNV (p = 0.048). CONCLUSION: A significant increase in mean drusen volume occurs in eyes in the preceding 12 months prior to conversion to neovascular AMD and this change is more significant in eyes with occult CNV.

Changes in volume of various retinal layers over time in early and intermediate age-related macular degeneration.

PURPOSE: To evaluate longitudinally volume changes in inner and outer retinal layers in early and intermediate age-related macular degeneration (AMD) compared to healthy control eyes using optical coherence tomography (OCT). METHODS: 71 eyes with AMD and 31 control eyes were imaged at two time points: baseline and after 2 years. Automated OCT layer segmentation was performed using OrionTM. This software is able to measure volumes of retinal layers with distinct boundaries including Retinal Nerve Fibre Layer (RNFL), Ganglion Cell-Inner Plexiform Layer (GCIPL), Inner Nuclear Layer (INL), Outer Plexiform Layer (OPL), Outer Nuclear Layer (ONL), Photoreceptors (PR) and Retinal Pigment Epithelium-Bruch's Membrane complex (RPE-BM). The mean retinal layer volumes and volume changes at 2 years were compared between groups. RESULTS: Mean GCIPL and INL volumes were lower, while PR and RPE-BM volumes were higher in AMD eyes than controls at baseline (all P < 0.05) and year 2 (all P < 0.05). In AMD eyes, RNFL and ONL volumes decreased by 0.0232 (P = 0.033) and 0.0851 (P = 0.001), respectively. In contrast, OPL and RPE-BM volumes increased in AMD eyes by 0.0391 (P = 0.000) and 0.0209 (P = 0.000) respectively. Moreover, there were significant differences in longitudinal volume change of OPL (P = 0.02), ONL (P = 0.008) and RPE-BM (P = 0.02) between AMD eyes and controls. CONCLUSIONS: There were abnormal retinal layer volumes and volume changes in eyes with early and intermediate AMD.