Multiple instance learning based classification of diabetic retinopathy in weakly-labeled widefield OCTA en face images.

Diabetic retinopathy (DR), a pathologic change of the human retinal vasculature, is the leading cause of blindness in working-age adults with diabetes mellitus. Optical coherence tomography angiography (OCTA), a functional extension of optical coherence tomography, has shown potential as a tool for early diagnosis of DR through its ability to visualize the retinal vasculature in all spatial dimensions. Previously introduced deep learning-based classifiers were able to support the detection of DR in OCTA images, but require expert labeling at the pixel level, a labor-intensive and expensive process. We present a multiple instance learning-based network, MIL-ResNet,14 that is capable of detecting biomarkers in an OCTA dataset with high accuracy, without the need for annotations other than the information whether a scan is from a diabetic patient or not. The dataset we used for this study was acquired with a diagnostic ultra-widefield swept-source OCT device with a MHz A-scan rate. We were able to show that our proposed method outperforms previous state-of-the-art networks for this classification task, ResNet14 and VGG16. In addition, our network pays special attention to clinically relevant biomarkers and is robust against adversarial attacks. Therefore, we believe that it could serve as a powerful diagnostic decision support tool for clinical ophthalmic screening.

Comparison of Stimulus Types for Retinotopic Cortical Mapping of Macular Disease.

Purpose: Retinotopic maps acquired using functional magnetic resonance imaging (fMRI) provide a valuable adjunct in the assessment of macular function at the level of the visual cortex. The present study quantitatively assessed the performance of different visual stimulation approaches for mapping visual field coverage. Methods: Twelve patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) were examined using high-resolution ultra-high field fMRI (Siemens Magnetom 7T) and microperimetry (MP; Nidek MP-3). The population receptive field (pRF)-based coverage maps obtained with two different stimulus techniques (moving bars, and rotating wedges and expanding rings) were compared with the results of MP. Correspondence between MP and pRF mapping was quantified by calculating the simple matching coefficient (SMC). Results: Stimulus choice is shown to bias the spatial distribution of pRF centers and eccentricity values with pRF sizes obtained from wedge/ring or bar stimulation showing systematic differences. Wedge/ring stimulation results show a higher number of pRF centers in foveal areas and strongly reduced pRF sizes compared to bar stimulation runs. A statistical comparison shows significantly higher pRF center numbers in the foveal 2.5 degrees region of the visual field for wedge/ring compared to bar stimuli. However, these differences do not significantly influence SMC values when compared to MP (bar <2.5 degrees: 0.88 ± 0.13; bar >2.5 degrees: 0.88 ± 0.11; wedge/ring <2.5 degrees: 0.89 ± 0.12 wedge/ring; >2.5 degrees: 0.86 ± 0.10) for the peripheral visual field. Conclusions: Both visual stimulation designs examined can be applied successfully in patients with GA. Although the two designs show systematic differences in the distribution of pRF center locations, this variability has minimal impact on the SMC when compared to the MP outcome.

Baseline predictors for subretinal fibrosis in neovascular age-related macular degeneration.

To find baseline predictors for subretinal fibrosis (SF) in neovascular age-related macular degeneration (nAMD). Forty-five eyes of 45 participants with treatment-naïve nAMD were consecutively enrolled and treated according to a standardized treat-and-extend protocol. Spectral-domain optical coherence tomography (OCT), color fundus photography and fluorescein angiography as well as novel imaging modalities polarization-sensitive OCT and OCT angiography (OCTA) were performed to detect SF after 1 year and find baseline predictors for SF development. Baseline OCTA scans were evaluated for quantitative features such as lesion area, vessel area, vessel junctions, vessel length, vessel endpoints and mean lacunarity. Additionally, the type of macular neovascularization, the presence of subretinal fluid, intraretinal fluid (IRF), subretinal hyperreflective material (SHRM), retinal hemorrhage as well as best-corrected visual acuity (BCVA) were evaluated. After 12 months 8 eyes (18%) developed SF. Eyes with SF had worse baseline BCVA (p = .001) and a higher prevalence of IRF (p = .014) and SHRM at baseline (p = .017). There was no significant difference in any of the evaluated quantitative OCTA parameters (p > .05) between eyes with and without SF. There were no quantitative baseline microvascular predictors for SF in our study. Low baseline BCVA, the presence of IRF and SHRM, however, are easily identifiable baseline parameters indicating increased risk.

THE SPECTRUM OF INTERNAL LIMITING MEMBRANE DISEASE IN ALPORT SYNDROME: A Multimodal Imaging Study.

PURPOSE: To characterize the spectrum of internal limiting membrane (ILM) disease in Alport syndrome using multimodal imaging, including widefield (WF) and ultra-widefield (UWF) modalities, and to report their relative prevalence according to the genetic pattern of inheritance. METHODS: Cross-sectional clinical study of patients diagnosed with Alport syndrome. All patients underwent UWF color photography and autofluorescence, WF-optical coherence tomography angiography and spectral-domain optical coherence tomography. Demographics, past medical and ophthalmic history, and genetic mutation history were collected. RESULTS: Forty-two eyes of 21 patients (11 men; age 36.6 ± 12.9 years) were included. Macular spectral-domain optical coherence tomography revealed ILM granularity, more frequent in X-linked Alport syndrome and corresponding to dot maculopathy on color fundus. Mid-peripheral spectral-domain optical coherence tomography scans revealed multilamellated ILM in eight eyes (19%), presumably progressive, which corresponded to a cavitary pattern on en-face OCT. En-face OCT revealed multiple areas of retinal nerve fiber layer dehiscence in the macula, overlapping with vascular lacunae on optical coherence tomography angiography, and a coarse arrangement of retinal nerve fiber layer above and below the temporal raphe in 20 eyes (52%). CONCLUSION: Multimodal imaging allowed for the detection/characterization of retinal findings (ILM granularity, progressive ILM lamellation, retinal nerve fiber layer dehiscence, vascular lacunae, and coarse arrangement of retinal nerve fiber layer toward the disc) as multifaceted manifestations of ILM disease in Alport syndrome.

Quantification of Fluid Resolution and Visual Acuity Gain in Patients With Diabetic Macular Edema Using Deep Learning: A Post Hoc Analysis of a Randomized Clinical Trial.

Importance: Large amounts of optical coherence tomographic (OCT) data of diabetic macular edema (DME) are acquired, but many morphologic features have yet to be identified and quantified. Objective: To examine the volumetric change of intraretinal fluid (IRF) and subretinal fluid (SRF) in DME during anti-vascular endothelial growth factor treatment using deep learning algorithms. Design, Setting, and Participants: This post hoc analysis of a randomized clinical trial, the Diabetic Retinopathy Clinical Research Network (protocol T), assessed 6945 spectral-domain OCT volume scans of 570 eyes from 570 study participants with DME. The original trial was performed from August 21, 2012, to October 18, 2018. This analysis was performed from December 7, 2017, to January 15, 2020. Interventions: Participants were treated according to a predefined, standardized protocol with aflibercept, ranibizumab, or bevacizumab with or without deferred laser. Main Outcomes and Measures: The association of treatment with IRF and SRF volumes and best-corrected visual acuity (BCVA) during 12 months using deep learning algorithms. Results: Among the 570 study participants (302 [53%] male; 369 [65%] white; mean [SD] age, 43.4 [12.6] years), the mean fluid volumes in the central 3 mm were 448.6 nL (95% CI, 412.3-485.0 nL) of IRF and 36.9 nL (95% CI, 27.0-46.7 nL) of SRF at baseline and 161.2 nL (95% CI, 135.1-187.4 nL) of IRF and 4.4 nL (95% CI, 1.7-7.1 nL) of SRF at 12 months. The presence of SRF at baseline was associated with a worse baseline BCVA Early Treatment Diabetic Retinopathy Study (ETDRS) score of 63.2 (95% CI, 60.2-66.1) (approximate Snellen equivalent of 20/63 [95% CI, 20/50-20/63]) in eyes with SRF vs 66.9 (95% CI, 65.7-68.1) (approximate Snellen equivalent, 20/50 [95% CI, 20/40-20/50]) without SRF (P < .001) and a greater gain in ETDRS score (0.5; 95% CI, 0.3-0.8) every 4 weeks during follow-up in eyes with SRF at baseline vs 0.4 (95% CI, 0.3-0.5) in eyes without SRF at baseline (P = .02) when adjusted for baseline BCVA. Aflibercept was associated with greater reduction of IRF volume compared with bevacizumab after the first injection (difference, 79.8 nL; 95% CI, 5.3-162.5 nL; P < .001) and every 4 weeks thereafter (difference, 10.4 nL; 95% CI, 0.7-20.0 nL; P = .004). Ranibizumab was associated with a greater reduction of IRF after the first injection compared with bevacizumab (difference, 75.2 nL; 95% CI, 1.4-154.7 nL; P < .001). Conclusions and Relevance: Automated segmentation of fluid in DME revealed that the presence of SRF was associated with lower baseline BCVA but with good response to anti-vascular endothelial growth factor therapy. These automated spectral-domain OCT analyses may be used clinically to assess anatomical change during therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT01627249.

Retinal and Choroidal Perfusion Status in the Area of Laser Scars Assessed With Swept-Source Optical Coherence Tomography Angiography.

Purpose: To evaluate the perfusion status of the retina and choriocapillaris in the area of laser scars on swept-source optical coherence tomography angiography (OCTA) images of eyes previously treated with panretinal photocoagulation (PRP). Methods: Cross-sectional exploratory analysis of swept-source OCTA images, which were retrospectively reviewed for laser scars. The appearance of the capillary networks in the area of previous laser were evaluated following a three-step grading system (normal/sparse/missing capillary network). The superficial and deep capillary plexus of the retina and the choriocapillaris were graded separately. Results: A total of 3140 laser scars in 54 eyes of 31 patients (13 female, mean age 57 ± 12 years) were included in this analysis. In the retina, 6.8% of the superficial and deep capillary network in the area evaluated appeared normal, 58% and 56% sparse, and 35% and 37% missing. Capillary dropout in the retina was not restricted to the area of prior laser treatment. The choriocapillaris decorrelation signal was either sparse (61%) or completely missing (38%) within the laser scar area. The perfusion of the choriocapillaris appeared normal in the area adjacent to laser scars. Conclusions: Capillary non-perfusion in the choriocapillaris was found within the laser scar area. Laser treatment seems to cause sustained non-perfusion of choriocapillaris in the area treated.

Atrophy of the central neuroretina in patients treated for diabetic macular edema.

PURPOSE: To examine the prevalence of central retinal atrophy in patients treated for diabetic macular edema (DME) in a clinical setting. METHODS: Retrospective data analysis of patients with DME, focusing on those who developed central retinal thinning after DME treatment at the Department of Ophthalmology, Medical University Vienna. Patient characteristics and clinical data including best-corrected visual acuity (BCVA), spectral domain optical coherence tomography and fluorescence angiography images were reviewed and DME treatment strategies analysed using descriptive statistics. The correlation between visual acuity and ocular, systemic or DME treatment factors was calculated using linear regression models and ancovas. RESULTS: A total of 6684 outpatient visits by 1437 patients with diabetes were analysed. Out of 149 patients, who had had a central subfield thickness (CST) below 200 µm, 32 (36 eyes) had previously been diagnosed with a centre involving DME with an average CST of 473 ± 103 µm and average visual acuity of 0.62 ± 0.44 logMAR at first presentation. At the time of central atrophy, 29 (81%) out of 36 eyes had a history of laser treatment, 11 (31%) a vitrectomy, 32 (88%) repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF; mean 5.3 ± 3.8) and 22 (61%) intravitreal corticosteroid injections (mean 2.5 ± 2.7). Visual function (0.67 ± 0.43 logMAR) at the time of atrophy was not significantly correlated to central retinal thickness (191 ± 7 µm) or any other ocular, systemic or treatment factors. CONCLUSIONS: Only 4% of patients treated for DME developed central retinal thinning in our observation period. On average, our atrophy patients had higher CST and lower BCVA when they first presented with DME compared to the overall DME cohort, and they received a combination of intravitreal injections and laser for DME treatment. Central retinal atrophy might not be attributed to excessive use of intravitreally applied anti-VEGF or any other DME therapy alone.

Correspondence between retinotopic cortical mapping and conventional functional and morphological assessment of retinal disease.

PURPOSE: The present study describes retinotopic mapping of the primary visual cortex using functional MRI (fMRI) in patients with retinal disease. It addresses the relationship between fMRI data and data obtained by conventional assessment including microperimetry (MP) and structural imaging. METHODS: Initial testing involved eight patients with central retinal disease (Stargardt disease, STGD) and eight with peripheral retinal disease (retinitis pigmentosa, RP), who were examined using fMRI and MP (Nidek MP-1). All had a secure clinical diagnosis supported by electrophysiological data. fMRI used population-receptive field (pRF) mapping to provide retinotopic data that were then compared with the results of MP, optical coherence tomography and fundus autofluorescence imaging. RESULTS: Full analysis, following assessment of fMRI data reliability criteria, was performed in five patients with STGD and seven patients with RP; unstable fixation was responsible for unreliable pRF measurements in three patients excluded from final analysis. The macular regions in patients with STGD with central visual field defects and outer retinal atrophy (ORA) at the macula correlated well with pRF coverage maps showing reduced density of activated voxels at the occipital pole. Patients with RP exhibited peripheral ORA and concentric visual field defects both on MP and pRF mapping. Anterior V1 voxels, corresponding to peripheral regions, showed no significant activation. Correspondence between MP and pRF mapping was quantified by calculating the simple matching coefficient. CONCLUSION: Retinotopic maps acquired by fMRI provide a valuable adjunct in the assessment of retinal dysfunction. The addition of microperimetric data to pRF maps allowed better assessment of macular function than MP alone. Unlike MP, pRF mapping provides objective data independent of psychophysical perception from the patient.

IMAGING OF VITELLIFORM MACULAR LESIONS USING POLARIZATION-SENSITIVE OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To examine the involvement of the retinal pigment epithelium (RPE) in the presence of vitelliform macular lesions (VML) in Best vitelliform macular dystrophy (BVMD), autosomal recessive bestrophinopathy, and adult-onset vitelliform macular degeneration using polarization-sensitive optical coherence tomography (PS-OCT). METHODS: A total of 35 eyes of 18 patients were imaged using a PS-OCT system and blue light fundus autofluorescence imaging. Pathogenic mutations in the BEST1 gene, 3 of which were new, were detected in all patients with BVMD and autosomal recessive bestrophinopathy. RESULTS: Polarization-sensitive optical coherence tomography showed a characteristic pattern in all three diseases with nondepolarizing material in the subretinal space consistent with the yellowish VML seen on funduscopy with a visible RPE line below it. A focal RPE thickening was seen in 26 eyes under or at the edge of the VML. Retinal pigment epithelium thickness outside the VML was normal or mildly thinned in patients with BVMD and adult-onset vitelliform macular degeneration but was diffusely thinned or atrophic in patients with autosomal recessive bestrophinopathy. Patients with autosomal recessive bestrophinopathy showed sub-RPE fibrosis alongside the subretinal VML. Polarization-sensitive optical coherence tomography was more reliable in assessing the localization and the integrity of the RPE than spectral domain OCT alone. On spectral domain OCT, identification of the RPE was not possible in 19.4% of eyes. Polarization-sensitive optical coherence tomography allowed for definite identification of the location of VML in respect to the RPE in all eyes, since it provides a tissue-specific contrast. CONCLUSION: Polarization-sensitive optical coherence tomography confirms in vivo the subretinal location of VML and is useful in the assessment of RPE integrity.

Association of Changes in Macular Perfusion With Ranibizumab Treatment for Diabetic Macular Edema: A Subanalysis of the RESTORE (Extension) Study.

Importance: Anti-vascular endothelial growth factor treatment is the first-line therapy in the treatment of center-involving diabetic macular edema. Data on capillary perfusion changes under repeated treatment in a possibly compromised vascular network are limited. Objective: To evaluate the association of repeated ranibizumab injections on macular perfusion in patients with diabetic macular edema. Design, Setting, and Participants: This study analyzed prospectively collected data from the 12-month RESTORE core study and the 24-month open label RESTORE extension study, which assessed the efficacy and safety of ranibizumab in patients with visual impairment due to diabetic macular edema. Of 345 patients with center-involving diabetic macular edema who had enrolled in the 12-month RESTORE core study, 240 entered the 24-month RESTORE extension study. Of these, 83 (34.6%) received ranibizumab, 83 (34.6%) received ranibizumab and laser combination therapy, and 74 (30.8%) received laser monotherapy in the first year of the study; 208 completed the 24-month extension study. Fluorescence angiography images were taken from each participant twice each year graded by Vienna Reading Center on severity of capillary loss in the parafoveal area, regularity of the foveal avascular zone outline, and measurement of the size of the foveal avascular zone, following a standardized protocol. Data analysis took place from July 2014 through December 2017. Main Outcomes and Measures: Change in 3 fluorescence angiography perfusion parameters over the course of treatment. Results: Mean (SD) patient age was 62.6 (8.8) years; 124 of 208 (59.2%) were male and 197 of 208 (94.6%) were white. The number of patients with definite altered foveal avascular zone regularity at baseline was 103 of 240 patients (42.9%); another 118 patients (49.2%) had questionably altered regularity at baseline. Definitive capillary loss was found in 65 of 240 patients (27.1%) at baseline. Mean (SD) foveal avascular zone size at baseline was 0.261 (0.232) mm2 in ranibizumab monotherapy, 0.231 (0.219) mm2 in ranibizumab and macular laser combination therapy, and 0.201 (0.13) mm2 in laser monotherapy. No treatment arm experienced significant increase in foveal avascular zone size at any time in the study period. At month 36, ranibizumab monotherapy resulted in a mean increase of 0.073 mm2 (95% CI, 0.005-0.142 mm2) and combination therapy resulted in a mean increase of 0.117 mm2 (95% CI, 0.045-0.188 mm2), but no changes were statistically significant. No changes occurred in foveal avascular zone regularity in any treatment group, and no differences were found in capillary loss around the fovea in the 3 treatment groups; neither element could be correlated with visual acuity or central retinal thickness. Conclusions and Relevance: Repeated ranibizumab treatment was not associated with impaired macular perfusion in our study cohort. Because our data do not suggest a harmful effect of anti-vascular endothelial growth factor therapy on capillary integrity, patients with severe microangiopathy and advanced capillary dropout should not be denied these treatments.

Multivendor Spectral-Domain Optical Coherence Tomography Dataset, Observer Annotation Performance Evaluation, and Standardized Evaluation Framework for Intraretinal Cystoid Fluid Segmentation.

Development of image analysis and machine learning methods for segmentation of clinically significant pathology in retinal spectral-domain optical coherence tomography (SD-OCT), used in disease detection and prediction, is limited due to the availability of expertly annotated reference data. Retinal segmentation methods use datasets that either are not publicly available, come from only one device, or use different evaluation methodologies making them difficult to compare. Thus we present and evaluate a multiple expert annotated reference dataset for the problem of intraretinal cystoid fluid (IRF) segmentation, a key indicator in exudative macular disease. In addition, a standardized framework for segmentation accuracy evaluation, applicable to other pathological structures, is presented. Integral to this work is the dataset used which must be fit for purpose for IRF segmentation algorithm training and testing. We describe here a multivendor dataset comprised of 30 scans. Each OCT scan for system training has been annotated by multiple graders using a proprietary system. Evaluation of the intergrader annotations shows a good correlation, thus making the reproducibly annotated scans suitable for the training and validation of image processing and machine learning based segmentation methods. The dataset will be made publicly available in the form of a segmentation Grand Challenge.

Intraretinal cysts are the most relevant prognostic biomarker in neovascular age-related macular degeneration independent of the therapeutic strategy.

BACKGROUND/AIMS: To investigate the impact of antiangiogenic monotherapy and photodynamic therapy (PDT) as add-on strategy on retinal morphology, and to analyse prognostic biomarkers for visual outcome and retreatment frequency in neovascular age-related macular degeneration (nAMD). METHODS: 255 patients participating in the MONT BLANC study were evaluated. Patients were randomised to receive as-needed ranibizumab monotherapy or combination therapy (verteporfin PDT and ranibizumab). Outcome measures included visual acuity (VA), retinal morphology assessed by optical coherence tomography and retreatment frequency. RESULTS: The proportion of scans showing intraretinal cysts (IRC) or subretinal fluid (SRF) decreased more intensively in the combination than in the monotherapy group. Pigment epithelial detachments (PED) decreased significantly only in the combination group. Patients with IRC presented the lowest initial VA, and IRC had the strongest negative predictive value for functional improvement in both groups. SRF showed a predictive value for a higher number of ranibizumab injections (combination, +0.9; monotherapy, +0.8) and a higher number of PDT treatments in the combination group (+0.3). PED was associated with a higher number of ranibizumab injections only in the monotherapy group (+1.2). CONCLUSIONS: Combination and monotherapy showed a distinct response pattern for morphological parameters in nAMD. IRC was the only relevant prognostic parameter for functional outcome. TRIAL REGISTRATION NUMBER: NCT00433017.

Morphologic parameters relevant for visual outcome during anti-angiogenic therapy of neovascular age-related macular degeneration.

PURPOSE: To identify the effects of anti-angiogenic therapy in neovascular age-related macular degeneration (AMD) in respect to morphologic type and time course and to identify prognostic factors for visual outcome on the basis of standardized optical coherence tomography (OCT) analysis. DESIGN: Subanalysis of a prospective, 12-month, multicenter, phase IIIb trial (Efficacy and Safety of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration [EXCITE]). PARTICIPANTS: A total of 353 treatment-naïve patients with subfoveal choroidal neovascularization (CNV) receiving quarterly or monthly ranibizumab therapy. METHODS: Patients were randomized to receive 0.3 mg quarterly, 0.5 mg quarterly, or 0.3 mg monthly doses of ranibizumab. Treatment comprised a loading phase of 3 consecutive monthly injections followed by a 9-month maintenance phase of monthly or quarterly injections. Best-corrected visual acuity (BCVA) was measured using the Early Treatment Diabetic Retinopathy Study protocol, and retinal morphology was assessed by Stratus OCT (Carl Zeiss Meditec, Dublin, CA). Imaging data were evaluated by certified examiners of the Vienna Reading Center using a standardized protocol. MAIN OUTCOME MEASURES: The BCVA was measured using ETDRS charts and retinal morphology was assessed by OCT. RESULTS: During the loading phase, there was a significant correlation between a reduction in central retinal thickness and an increase in BCVA (P < 0.001), which decreased during the maintenance phase in all treatment arms. The proportion of patients showing retinal morphologic changes, such as intraretinal cysts (IRCs), subretinal fluid (SRF), and pigment epithelial detachments (PEDs), decreased significantly in all groups (P < 0.001), more intensively in the 0.5 mg quarterly than in both 0.3 mg groups. Intraretinal cysts resolved most rapidly followed by SRF, whereas PED decreased at a slower rate and intensity. Patients with IRC at baseline had lower BCVA levels that remained lower over the entire study period, whereas recurrence of IRC during follow-up showed no additional negative effect on function. Baseline SRF had no effect on visual recovery; however, recurrence of SRF during follow-up showed a tendency for an additional negative effect on function (P = 0.06). Baseline PED showed a negative influence on visual outcome only in combination with IRC and SRF. CONCLUSIONS: There is a distinct response pattern and time course of morphologic parameters associated with anti-vascular endothelial growth factor therapy in neovascular AMD. Specific alterations, such as IRC, SRF, and PED, as baseline or follow-up features are significantly influencing the potential for visual gain.

Characterization of stargardt disease using polarization-sensitive optical coherence tomography and fundus autofluorescence imaging.

PURPOSE: To identify disease-specific changes in Stargardt disease (STGD) based on imaging with polarization-sensitive spectral-domain optical coherence tomography (PS-OCT) and to compare structural changes with those visible on blue light fundus autofluorescence (FAF) imaging. METHODS: Twenty-eight eyes of 14 patients diagnosed with STGD were imaged using a novel high-speed, large-field PS-OCT system and FAF (excitation 488 nm, emission > 500 nm). The ophthalmoscopic phenotype was classified into three groups. ABCA4 mutation testing detected 15 STGD alleles, six of which harbor novel mutations. RESULTS: STGD phenotype 1 (12 eyes) showed sharply delineated areas of absent RPE signal on RPE segmentation B-scans of PS-OCT correlating with areas of hypofluorescence on FAF. Adjacent areas of irregular fluorescence correlated with an irregular RPE segmentation line with absence of overlaying photoreceptor layers. Eyes characterized on OCT by a gap in the subfoveal outer segment layer (foveal cavitation) showed a normal RPE segmentation line on PS-OCT. Hyperfluorescent flecks on FAF in phenotype 2 STGD (8 eyes) were identified as clusters of depolarizing material at the level of the RPE. Distribution of flecks could be depicted on RPE elevation maps. An increased amount of depolarizing material in the choroid was characteristic for STGD Phenotype 3 (8 eyes). CONCLUSIONS: PS-OCT together with FAF identified characteristic patterns of changes in different stages of the disease. PS-OCT is a promising new tool for diagnosis and evaluation of future treatment modalities in STGD.

Coexistence of KCNV2 associated cone dystrophy with supernormal rod electroretinogram and MFRP related oculopathy in a Turkish family.

BACKGROUND AND AIM: To describe the clinical and genetic characteristics of a mother and her son presenting with two distinct and rare forms of retinal degeneration. METHODS: Investigations in both patients comprised spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence imaging, non-contact biometry, ultrasonography, electroretinography (ERG) and analysis of the mutational status of the KCNV2 and MFRP genes in genomic DNA. RESULTS: The clinical course and typical ERG pattern indicated a 'cone dystrophy with supernormal rod electroretinogram' in the proband, and SD-OCT demonstrated a subfoveal optical gap with loss of the inner segment/outer segment junction line. The proband was homozygous for a c.782C>A (p.Ala261Asp) mutation in KCNV2. Her son's axial length was shortened with refractive errors of +16.75 dioptres in the right and +14.0 dioptres in the left eye; ERG evidenced a rod-cone dystrophy, OCT showed central macular thickening with cystoid changes and ultrasonography revealed optic disc drusen. MFRP analysis disclosed a 1 bp deletion (c.498delC) that predicts a truncated protein. CONCLUSIONS: Two distinct ocular phenotypes with pathogenic mutations in two different genes segregated in this family. The coexistence of two independent autosomal recessive disorders should be considered even when dealing with diseases that bear low carrier frequencies in the general population.

In vivo identification of alteration of inner neurosensory layers in branch retinal artery occlusion.

BACKGROUND/AIMS: To characterise the extension and progression of alteration of neurosensory layers following acute and chronic branch retinal artery occlusion (BRAO) in vivo using spectral-domain optical coherence tomography. METHODS: In this observational case series, eight eyes with acute BRAO and nine eyes with chronic BRAO were analysed using a Spectralis Heidelberg Retina Angiograph (HRA)+optical coherence tomography system including eye tracking. Patients with acute BRAO were examined within 36±5 h after primary event and at weekly/monthly intervals thereafter. Segmentation measurements of all individual neurosensory layers were performed on single A-scans at six locations in affected and corresponding non-affected areas. The thickness values of the retinal nerve fibre layer together with the ganglion cell layer (NFL/GCL), inner plexiform layer (IPL), inner nuclear layer together with outer plexiform layer (INL/OPL), outer nuclear layer (ONL), and photoreceptor layers together with the retinal pigment epithelium (PR/RPE) were measured and analysed. RESULTS: Segmentation evaluation revealed a distinct increase in thickness of inner neurosensory layers including the NFL/GCL (35%), IPL (80%), INL/OPL (48%) and mildly the ONL by 21% in acute ischaemia compared with corresponding layers in non-ischaemic areas. Regression of intraretinal oedema was followed by persistent retinal atrophy with loss of differentiation between IPL and INL/OPL at month 2. In contrast, the ONL and subjacent PR/RPE retained their physiological thickness in patients with chronic BRAO. CONCLUSION: In vivo assessment of retinal layer morphology allows a precise identification of the pathophysiology in retinal ischaemia.

Evaluation of optical coherence tomography findings in age-related macular degeneration: a reproducibility study of two independent reading centres.

BACKGROUND/AIMS: To determine the reproducibility among readers of two independent certified centres, the Vienna Reading Center (VRC) and the University of Wisconsin-Madison Reading Center (UW-FPRC) for optical coherence tomography (OCT) images in age-related macular degeneration (AMD). METHODS: Fast macular thickness scans and 6 mm cross hair scans were obtained from 100 eyes with all subtypes of AMD using Stratus OCT. Consensus readings were performed by two certified OCT readers of each reading center using their grading protocol. Common variables of both grading protocols, such as presence of cystoid spaces, subretinal fluid, vitreomacular traction and retinal pigment epithelial detachment, were compared using κ statistics. In addition, the intraclass correlation coefficient (ICC) was calculated for centre point thickness (CPT) of values re-measured manually in the presence of alignment errors. RESULTS: The reproducibility was dependent on the variable measured with a κ value of 0.81 for the presence of cystoid spaces, 0.78 for the presence of subretinal fluid and 0.795 for the presence of vitreomacular traction. The lowest reproducibility was found for the presence of retinal pigment epithelial detachment with a κ value of 0.51. The CPT was re-measured in 29 out of 100 scans at both sites with an ICC of the re-measured thicknesses of 0.92. CONCLUSION: OCT scan data are crucial in monitoring treatment efficacy in AMD clinical trials. For comparison of results obtained by different reading centers, the inter-reading center reproducibility is essential. Although the reproducibility is generally high, the reliability depends on the selected morphological parameters.

Retinal optical coherence tomography: past, present and future perspectives.

Optical coherence tomography (OCT) has undergone substantial changes since its first use in the 1990s. Although the first generation of OCT systems heralded a new era in the non-invasive diagnostic options in ophthalmology, they did not reveal much detail. Later devices offered more information and helped in the diagnosis and treatment of a variety of pathological conditions, primarily of the retina. With today's spectral-domain type models ophthalmologists are offered a comprehensive tool with the opportunity for early diagnosis and precise monitoring of patients with retinal and glaucomatous pathologies. However, as experience with these new devices grows and demands by clinicians and researchers rise, further improvements need to be addressed. Future developments in the improvement of the transverse resolution and extension of the penetration depth are to be expected. New modalities such as polarisation sensitive OCT (PS-OCT) or Doppler OCT are now in use and promise additional insights in the properties of physiological and pathological tissue. While PS-OCT reveals further detail in alterations of the retinal pigment epithelium, Doppler OCT gives additional information about blood flow measurements. With these and further new developments, OCT will continue to be an invaluable instrument in the armamentarium of modern ophthalmology.