Philipp Roberts

Drusen volume development over time and its relevance to the course of age-related macular degeneration

Aims To quantify the change in drusen volume over time and identify its prognostic value for individual risk assessment. Methods A prospective observational study over a minimum of 3 years and maximum of 5 years and follow-up examination every 3 months was conducted at the ophthalmology department of the Medical University of Vienna. 109 patients presenting early and intermediate age-related macular degeneration (AMD) were included, of which 30 patients concluded a regular follow-up for at least 3 years. 50 eyes of 30 patients were imaged every 3 months using spectral-domain and polarisation-sensitive optical coherence tomography (OCT). Drusen volume was measured using an automated algorithm. Data of a 6-month follow-up were segmented manually by expert graders. Results Gradings from 24 000 individual B-scans showed solid correlation between manual and automated segmentation with an initial mean drusen volume of 0.17 mm3. The increase in drusen volume was shown to be comparable among all eyes, and a model for long-term drusen volume development could be fitted as a cubic polynomial function and an R2=0.955. Spontaneous drusen regression was observed in 22 of 50 eyes. In this group, four eyes developed choroidal neovascularisation and three geographic atrophy. Conclusions Drusen volume increase over time can be described by a cubic function. Spontaneous regression appears to precede conversion to advanced AMD. OCT might be a promising tool for predicting the individual risk of progression of AMD.

Large-field high-speed polarization sensitive spectral domain OCT and its applications in ophthalmology

We present a novel spectral domain polarization sensitive OCT system (PS-OCT) that operates at an A-scan rate of 70 kHz and supports scan angles of up to 40° × 40°. The high-speed imaging allows the acquisition of up to 1024 × 250 A-scans per 3D scan, which, together with the large field of view, considerably increases the informative value of the images. To demonstrate the excellent performance of the new PS-OCT system, we imaged several healthy volunteers and patients with various diseases such as glaucoma, AMD, Stargardt’s disease, and albinism. The results are compared with clinically established methods such as scanning laser polarimetry and autofluorescence.

Morphologic and functional evaluations during development, resolution, and relapse of uveitis-associated cystoid macular edema.

Objectives: To describe progression and resolution of uveitis-associated cystoid macular edema (uvCME) using spectral-domain optical coherence tomography and find predictive factors for successful intravitreal triamcinolone acetonide (IVTA) therapy. Methods: Twenty-nine eyes with treatment-naive uvCME were examined before and at 5 scheduled visits within 3 months after intravitreal triamcinolone acetonide administration. Distribution, resolution, relapse, and development of uvCME were evaluated using spectral-domain optical coherence tomography to describe morphology, progression, and relapse according to a standardized reading protocol. Applying repeated measures analysis of variance, morphologic findings were evaluated as predictive factors of the treatment outcome. Results: At baseline, 89.3% presented with focal CME; 65.6% had outer nuclear/Henley’s layer and inner nuclear layer cysts. Following intravitreal triamcinolone acetonide administration, cysts of outer nuclear/Henley’s layer diminished before those of inner nuclear layer (P = 0.0004). Small-pointed subretinal detachment (SRD) resolution synchronized with inner nuclear layer cyst extinction, whereas dome-shaped SRD resolution lagged behind (P = 0.014). Relapses of CME appeared in 71.4% of eyes with parafoveal inner nuclear layer cysts. Cysts of outer nuclear/Henley’s layer were present in an additional 28.6%. None of the eyes developed SRD during CME relapse. The main effect variables “SRD” and “absence of epiretinal membrane” were associated with greater best-corrected visual acuity improvement (P = 0.05 and P = 0.047), whereas the side effect variables “CME duration”, “age,” and “uveitis location” had no additional effect on best-corrected visual acuity. Baseline SRD predicted a relapse-free clinical course within the observational period (P = 0.025). Conclusion: Different morphologic patterns in uvCME may represent different stages in uvCME progression, and initial morphologic appearance can be linked to the clinical prognosis after the treatment.

One Year Follow-up of Functional Recovery in Neovascular AMD During Monthly Anti-VEGF Treatment

PURPOSE To identify neurosensory recovery, testing different functional variables during monthly intravitreal standard anti-vascular endothelial growth factor (VEGF) therapy in neovascular age-related macular degeneration (AMD). DESIGN Prospective interventional cohort study. METHODS Sixty-four treatment-naïve neovascular AMD patients with subfoveal lesions were treated and examined monthly for distance visual acuity, reading acuity, maximum reading speed, and contrast sensitivity and with microperimetry evaluating the percentage of absolute and relative scotoma and mean central retinal sensitivity weighted by area. Improvements in reading acuity, distance acuity, reading speed, contrast sensitivity, mean central retinal sensitivity, and scotoma area in dependence of age, lesion type, lesion size, and mean central retinal sensitivity were evaluated by a random-slope and random-intercept model. Recovery pattern of parameters was compared by correlating the individual slopes of each variable. RESULTS Initially, a rapid short-term effect of anti-VEGF treatment was documented throughout all functional variables. Progressive functional gain over 1 year was observed for distance visual acuity (P = .011), contrast sensitivity (P ≤ .0001), and mean central retinal sensitivity (P ≤ .0001), but not for reading acuity (P = .31) and maximum reading speed (P = .94). Decrease of absolute scotoma area missed statistical significance over time (P = .053) and also fixation stability did not improve (P = .08). However, lesion size influenced the course of absolute scotoma area (P = .0015), while lesion type had no effect on any visual function variable evaluated. The individual slopes of reading acuity and distance visual acuity showed a moderate correlation; however, all other variables showed only a weak or no significant correlation among each other. CONCLUSION Visual recovery in anti-VEGF therapy is reflected in a characteristic pattern of functional changes over time, whereas distance visual acuity does not seem to comprehensively reflect overall visual function gain.

Motion artifact and speckle noise reduction in polarization sensitive optical coherence tomography by retinal tracking

We present a novel polarization sensitive optical coherence tomography (PS-OCT) system with an integrated retinal tracker. The tracking operates at up to 60 Hz, correcting PS-OCT scanning positions during the acquisition to avoid artifacts caused by eye motion. To demonstrate the practical performance of the system, we imaged several healthy volunteers and patients with AMD both with B-scan repetitions for frame averaging and with 3D raster scans. Under large retinal motions with up to 1 mm amplitude at 0.5 ~a few Hz frequency range, motion artifact suppression in the PS-OCT images as well as standard deviation noise reduction in the frame averaged retardation images are presented.

Correlation of OCT Characteristics and Retinal Sensitivity in Neovascular Age-Related Macular Degeneration in the Course of Monthly Ranibizumab Treatment

PURPOSE To evaluate the functional treatment response 3 months and 12 months after monthly ranibizumab in neovascular age-related macular degeneration (NAMD). METHODS Twenty-six eyes showing treatment-naïve NAMD were examined with the Heidelberg Spectralis OCT (SD-OCT) and the Nidek MP-1 microperimeter (MP) at baseline, after 3 months, and after 12 months of monthly ranibizumab therapy. Each test point of light sensitivity was transferred to the corresponding location on SD-OCT, and subsequently the microperimetric results were evaluated with respect to the following oct findings: neovascular complex (NVC), subretinal fluid (SRF), intraretinal fluid (IRF), intraretinal cystoid space (IRCS), serous pigment epithelium detachment (SPED), and fibrovascular pigment epithelium detachment (FPED). RESULTS Loci of an initial NVC improved significantly from a mean retinal sensitivity value of 2.6 dB ± 0.8 dB at baseline to 7.4 dB ± 0.9 dB (P < 0.0001) at month 12. Initial SRF, IRF, and IRCS improved significantly from a mean value of 5.1 dB ± 0.9 dB to 12.4 dB ± 0.9 dB (P < 0.0001), 4.0 dB ±1.0 dB to 9.3 dB ± 0.9 dB (P < 0.0001), and 3.4 dB ± 0.9 dB to 8.2 dB ± 0.9 dB (P < 0.0001), respectively. An initial SPED improved significantly from a mean retinal sensitivity value of 1.9 dB ± 1.1 dB at baseline to 9.4 dB ± 1.1 dB (P < 0.0001) at month 12; a FPED improved significantly from 5.2 dB ± 0.9 dB at baseline to 7.6 dB ± 0.9 dB (P < 0.0001) at month 12. CONCLUSIONS Functional benefit could be detected at all locations of macular pathology, with a lower benefit in the case of FPED and in the case of additional IRCS, and a marked benefit for all types of macular edema. (https://eudract.ema.europa.eu/, number 2006-005684-26.).

Quantifying Microvascular Abnormalities With Increasing Severity of Diabetic Retinopathy Using Optical Coherence Tomography Angiography

Purpose We quantified retinal and choriocapillaris microvascular changes in healthy control eyes and different stages of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). Methods This retrospective cross-sectional study included 137 eyes of 86 patients with different stages of DR and 44 eyes of 26 healthy age-matched controls. Participants were imaged with a commercial OCTA device (RTVue-XR Avanti). We analyzed the superficial (SCP) and deep (DCP) retinal capillary plexus, the full retina, and choriocapillaris for the following OCTA parameters: foveal avascular zone, vessel density, percent area of nonperfusion (PAN), and adjusted flow index (AFI). We adjusted for age, sex, and the correlation between eyes of the same study participant in our statistical models. Results All OCTA parameters showed a significant linear correlation with DR severity (P < 0.05) in the univariate models except for AFI measured in the SCP and these correlations remained significant after correcting for covariates. Compared to the other capillary layers, the AFI at the DCP decreased significantly with DR severity. When comparing individual disease severity groups as categories, eyes of subjects with diabetes without DR had significantly increased PAN and AFI in the SCP compared to healthy subjects (P < 0.05). Conclusions Retinal and choriocapillaris vascular nonperfusion in OCTA is correlated significantly with disease severity in eyes with DR. Higher flow in the SCP may be an early marker of diabetic microvascular changes before clinical signs of DR. The steep decline of blood flow in the DCP with increasing DR severity suggests that alterations at the DCP warrant further investigation.

Relationship of retinal morphology and retinal sensitivity in the treatment of neovascular age-related macular degeneration using aflibercept.

PURPOSE To relate the functional response to distinct morphological features of the retina during aflibercept treatment for neovascular AMD (nAMD). METHODS A total of 726 retinal locations in 22 consecutive eyes presenting with treatment-naive nAMD underwent a standardized examination with spectral-domain optical coherence tomography (SD-OCT) and topographic microperimetry (MP) at baseline, after 3 and 12 months of continuous intravitreal aflibercept therapy. The retinal sensitivity at each stimulus location was registered to the corresponding location on SD-OCT morphology. Subsequently, the microperimetric responses were evaluated with respect to the following underlying SD-OCT features: neovascular complex (NVC), subretinal fluid (SRF), intraretinal fluid (IRF), intraretinal cystoid space (IRC), serous pigment epithelium detachment (sPED), and fibrovascular pigment epithelium detachment (fPED). RESULTS Baseline sensitivity was reduced to mean values of 1.8 dB in NVC, 2.2 dB in IRC, 2.8 dB in IRF, 2.6 dB in sPED, 3.6 dB in SRF, and 4.6 dB in fPED. Improvements in retinal sensitivity were most pronounced during the initial 3-month interval, when significant recovery was documented for SRF and sPED with +4.0/5.5 dB (P < 0.0001) and to a lesser extent for IRF, IRC, fPED, with +1.1, 1.7, 2.3 dB, respectively. From month 3 to 12, the additional benefit ranged from 0.3 to 1.0 dB (P > 0.05 for each category). CONCLUSIONS Significant functional benefits following intravitreal aflibercept treatment could be detected over all defined morphological pathologies. The level of improvement varied dependent on the associated feature with the best prognosis for visual improvement in SRF and sPED and least with intraretinal fluid and particularly intraretinal cysts.

Retinal Pigment Epithelial Features in Central Serous Chorioretinopathy Identified by Polarization-Sensitive Optical Coherence Tomography

PURPOSE To determine the subclinical RPE lesions detected by tissue selective polarization-sensitive optical coherence tomography (PS-OCT) in eyes with central serous chorioretinopathy (CSC) and to compare PS-OCT findings to current imaging standards. METHODS In this prospective observational case series, individuals with unilateral or bilateral active CSC were imaged using PS-OCT at baseline and after resolution of serous retinal detachment. Features seen on PS-OCT were compared with corresponding lesions as seen on conventional, intensity-based spectral-domain OCT (SD-OCT), fluorescein angiography, and indocyanine green angiography (ICGA). Features of RPE evaluated by PS-OCT were as follows: area and volume of pigment epithelium detachment (PED), presence of RPE aggregations, RPE skip lesions, RPE thickening, and RPE atrophy. RESULTS Twenty-five study eyes and 23 fellow eyes of 25 participants (2 women, 23 men; mean age ± standard deviation = 40.5 ± 7.4 years) were included and followed for 6.1 ± 3 months. Study eyes and fellow eyes with recurrent CSC showed more RPE abnormalities in PS-OCT than eyes with acute CSC, which correlated well with lesions in ICGA. Closure of the leakage site was observed only in eight (32%) eyes after resolution of subretinal fluid (SRF). All study eyes showed widespread RPE aggregates and 23 (92%) eyes showed RPE skip lesions after resolution of SRF. CONCLUSIONS Features of RPE indicative of previous episodes of CSC detected by PS-OCT correspond well to choroidal lesions in ICGA. In addition, noninvasive PS-OCT imaging enables detection of RPE microrips and aggregations invisible to clinical examination or SD-OCT, thus providing valuable information about disease processes in vivo.

Chorioretinal Lesions in a Case of Melanoma-Associated Retinopathy Treated With Pembrolizumab.

Importance In recent years, the treatment of patients with advanced cutaneous melanoma has undergone substantial changes. Patients can now be offered treatment with immune checkpoint inhibitors, which are capable of increasing patient survival. However, these new treatments are associated with immune-related adverse effects that can involve different organ systems, including the eye. Observations We describe the case of a patient who received a diagnosis of metastatic cutaneous melanoma and developed melanoma-associated retinopathy with unanticipated fundus findings while receiving treatment with the immune checkpoint inhibitor pembrolizumab. Chorioretinal scars with pigment accumulations developed in the retinal periphery in both eyes. Conclusions and Relevance Immune checkpoint inhibitors, which are now being used more commonly for patients with advanced stages of melanoma, can exacerbate autoimmune diseases in patients with underlying clinical or latent autoimmunity. Clinicians should be aware of atypical eye findings, including chorioretinal scars.