Ute Wolf-Schnurrbusch

Morphologic Changes in Patients with Geographic Atrophy Assessed with a Novel Spectral OCT-SLO Combination

PURPOSE To investigate the appearance of geographic atrophy in high-resolution optical coherence tomography (OCT) images, the fundus autofluorescence (FAF) pattern, and infrared images simultaneously recorded with a novel combined OCT-scanning laser ophthalmology (SLO) system. METHODS Patients aged over 50 years with geographic atrophy secondary to dry age-related macular degeneration (ARMD) were assessed in a prospective cross-sectional study by means of simultaneous spectral OCT-SLO (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany). The integrity of the retinal layers was analyzed in the apparently normal areas, the junctional zone between the normal retina and the geographic atrophy, and the atrophic area. The presence and integrity of the external limiting membrane, the photoreceptor inner segments, the outer segments, and the retinal pigment epithelium were assessed. RESULTS Fifty-two eyes of 52 patients (28 women, 24 men) aged 51 to 92 years were examined. Retinal layer alterations were documented, not only in atrophic zones, but also in junctional zones surrounding the geographic atrophy. Disintegration of the retinal layers began in the RPE and adjacent retinal layers, such as the photoreceptor inner and outer segments and external limiting membrane. CONCLUSIONS Novel imaging modalities will provide further valuable insight into ARMD pathogenesis. The key to understanding the morphologic change lies in in vivo depiction of retinal layers by spectral OCT technology in combination with other imaging modalities such as FAF.

Effects of ranibizumab in patients with subfoveal choroidal neovascularization attributable to age-related macular degeneration.

PURPOSE To demonstrate not only prevention of vision loss but also improvement in best-corrected visual acuity (BCVA) after treatment with ranibizumab on a variable-dosing regimen over 24 months in patients with age-related macular degeneration (AMD). DESIGN Interventional case series. METHODS SETTING Institutional. STUDY POPULATION One hundred and thirty-eight eyes of 138 patients treated intravitreally with 0.5 mg ranibizumab (Lucentis; Novartis, Basel, Switzerland). Age above 50 years, BCVA 0.2 to 1.2 logarithm of the minimal angle of resolution (logMAR), primary or recurrent subfoveal choroidal neovascularization (CNV) secondary to AMD. OBSERVATION PROCEDURES After single initial treatment, monthly follow-up examination. Retreatment in case of one of the following: sign of subretinal fluid or intraretinal edema, increase in central retinal thickness (CRT) on optical coherence tomography (OCT), active CNV on fluorescein angiography, increase of metamorphopsia, and loss of BCVA > 5 letters on Early Treatment Diabetic Retinopathy Study (ETDRS) chart. MAIN OUTCOME MEASURES Compared with baseline: proportion of eyes gaining > or = 15 letters, proportion of eyes losing or gaining < 15 letters, change in CRT. RESULTS After 24 months, 30% of eyes gained > or = 15 letters. After 24 months, 55% of eyes lost or gained < 15 letters. Mean CRT of 386 +/- 145 microm at baseline was significantly reduced to 211 +/- 39 microm after 24 months (P = .036). Mean injection number per patient was 5.6 +/- 2.9 and 4.3 +/- 3.8 from baseline to month 12 and month 12 to 24, respectively. CONCLUSION Intravitreal ranibizumab on a variable-dosing regimen was effective in significantly increasing mean BVCA and reducing CRT. This beneficial outcome was achieved with a low-rate of mild ocular adverse effects among our patients.

Spectral-Domain Optical Coherence Tomography Use in Macular Diseases: A Review

The introduction of spectral-domain optical coherence tomography (SD-OCT) has improved the clinical value for assessment of the eyes with macular disease. This article reviews the advances of SD-OCT for the diagnostic of various macular diseases. These include vitreomacular traction syndrome, cystoid macular edema/diabetic macular edema, epiretinal membranes, full-thickness macular holes, lamellar holes, pseudoholes, microholes, and schisis from myopia. Besides offering new insights into the pathogenesis of macular abnormalities, SD-OCT is a valuable tool for monitoring macular disease.

Decreased Visual Function after Patchy Loss of Retinal Pigment Epithelium Induced by Low-Dose Sodium Iodate

PURPOSE To correlate damage to the retinal pigment epithelium (RPE) with decreased visual function after the systemic administration of sodium iodate (NaIO(3)). METHODS Damage was produced in mice by injection of 15, 25, or 35 mg/kg NaIO(3). Visual function was assessed with the cued water maze (WM) behavioral test and the optokinetic reflex (OKR) measurement at different times after injection. Autofluorescence in whole eye flatmounts was quantified, and hematoxylin and eosin staining of paraffin sections was performed to assess changes in the outer retina. RESULTS After 15 mg/kg NaIO(3), cued WM test results were normal, whereas OKR measurements were significantly decreased at all times. Focal RPE loss began on day 21, but no significant damage to the outer nuclear layer was observed. After 25 mg/kg NaIO(3), the cued WM test was transitionally reduced and the OKR measurement again decreased at all times. Large areas of RPE loss occurred on day 14 with a reduced outer nuclear layer on the same day. With 35 mg/kg NaIO(3), the cued WM test was reduced beginning on day 14 with complete obliteration of the OKR beginning on day 3, large areas of RPE loss on the same day, and a reduced outer nuclear layer on day 7. CONCLUSIONS Stable, patchy RPE loss was observed with a low concentration of NaIO(3). The OKR measurement showed changes in visual function earlier than the cued WM test and before histologic findings were observed.

The IS/OS Junction Layer in the Natural History of Type 2 Idiopathic Macular Telangiectasia

PURPOSE To document the progression of a break in the photoreceptor inner segment/outer segment (IS/OS) junction layer and its functional correlates over time in the natural history of type 2 idiopathic macular telangiectasia (type 2 MacTel). METHODS Patients with at least 1 year of follow-up were selected from the MacTel Study. En face images were created by manual segmentation of the IS/OS junctional line in volume scans acquired using a spatial-domain optical coherence tomography retinal imaging unit. Retinal sensitivity thresholds were determined using a retinal microperimeter unit. Aggregate retinal sensitivity loss within IS/OS lesions was calculated. Changes over time in an area of IS/OS defects and retinal sensitivity were analyzed. RESULTS thirty-nine eyes of 23 patients (mean age: 62.3 ± 9.2 years) were analyzed. Mean follow-up time was 1.9 years (range: 1-3 years). Mean IS/OS break area at baseline was 0.575 mm(2) (SE = 0.092, 95% confidence interval [CI]: 0.394-0.756 mm(2)). The cluster-adjusted mean annual progression rate in IS/OS break area was 0.140 mm(2) (SE = 0.040, 95% CI: 0.062-0.218 mm(2), P < 0.001). Mean aggregate retinal sensitivity loss was at baseline 28.56 dB (SE = 5.43, 95% CI: 17.32-39.80 dB, n = 28), a positive correlation with IS/OS lesion area was present (P < 0.001). The mean annual rate of change in aggregate sensitivity loss was 5.14 dB (SE = 1.51, 95% CI: 2.19-8.10 dB, P < 0.001, n = 37), a significant correlation with lesion area increase was found (P = 0.006). CONCLUSIONS Both IS/OS break area and rate of enlargement correlate with aggregate retinal sensitivity loss in type 2 MacTel. En face OCT imaging of the IS/OS layer provides a functionally relevant method for documenting disease progression in type 2 MacTel.

Quantitative analysis of fluorescence lifetime measurements of the macula using the fluorescence lifetime imaging ophthalmoscope in healthy subjects.

PURPOSE Fundus autofluorescence (FAF) cannot only be characterized by the intensity or the emission spectrum, but also by its lifetime. As the lifetime of a fluorescent molecule is sensitive to its local microenvironment, this technique may provide more information than fundus autofluorescence imaging. We report here the characteristics and repeatability of FAF lifetime measurements of the human macula using a new fluorescence lifetime imaging ophthalmoscope (FLIO). METHODS A total of 31 healthy phakic subjects were included in this study with an age range from 22 to 61 years. For image acquisition, a fluorescence lifetime ophthalmoscope based on a Heidelberg Engineering Spectralis system was used. Fluorescence lifetime maps of the retina were recorded in a short- (498-560 nm) and a long- (560-720 nm) spectral channel. For quantification of fluorescence lifetimes a standard ETDRS grid was used. RESULTS Mean fluorescence lifetimes were shortest in the fovea, with 208 picoseconds for the short-spectral channel and 239 picoseconds for the long-spectral channel, respectively. Fluorescence lifetimes increased from the central area to the outer ring of the ETDRS grid. The test-retest reliability of FLIO was very high for all ETDRS areas (Spearmans ρ = 0.80 for the short- and 0.97 for the long-spectral channel, P < 0.0001). Fluorescence lifetimes increased with age. CONCLUSIONS The FLIO allows reproducible measurements of fluorescence lifetimes of the macula in healthy subjects. By using a custom-built software, we were able to quantify fluorescence lifetimes within the ETDRS grid. Establishing a clinically accessible standard against which to measure FAF lifetimes within the retina is a prerequisite for future studies in retinal disease.

Retinal Crystals in Type 2 Idiopathic Macular Telangiectasia

PURPOSE To characterize the phenotype and investigate the associations of intraretinal crystalline deposits in a large cohort with type 2 idiopathic macular telangiectasia (MacTel). DESIGN Case-control study. PARTICIPANTS Patients with and without retinal crystals from the Macular Telangiectasia Project, an international multicenter prospective study of type 2 MacTel. METHODS Grading of stereoscopic 30-degree color fundus (CF), confocal blue light reflectance (CBR), red-free (RF), and infrared (IR) images was performed according to the MacTel Natural History Study protocol and staged using the classification system devised by Gass and Blodi. Spectral domain-optical coherence tomography (SD-OCT) and adaptive optics imaging were used for a finer analysis of the phenotype. Associations between crystals and other characteristics of the disease, as well as potential risk factors, were investigated. MAIN OUTCOME MEASURES Presence of crystals, fundus signs of MacTel, clinical characteristics, and presence of potential risk factors of MacTel. RESULTS Of 443 probands enrolled in the MacTel study, 203 (46%) had crystalline deposits present; 60% of the cases were bilateral at baseline. Eyes with crystals had a mean letter score of 70.7 (standard deviation [SD] = 15.9), whereas those without crystals had a mean letter score of 66.5 (SD = 15.5, P < 0.001). Crystals were present at all stages of the disease and showed high reflectivity within a wide wavelength range. They were located at the anterior surface of the nerve fiber layer, arranged along the nerve fibers, within an annular area centered on the fovea. Significant associations of crystalline deposits were found with a loss of retinal transparency, macular pigment optical density (MPOD) loss, fluorescein leakage, retinal thickness, and a break in the inner segment/outer segment junction line. Associations with environmental risk factors were not found. CONCLUSIONS Intraretinal crystals are a frequent phenomenon associated with type 2 MacTel. They may appear at all stages and aid in the early diagnosis of the disease. Their morphology further implicates Müller cells in the pathogenesis of the disease. Insight into their physical and chemical properties may provide clues to the metabolic pathways involved in the pathogenesis of the disease. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Small dense particles in the retina observable by spectral-domain optical coherence tomography in age-related macular degeneration.

PURPOSE To observe detailed changes in neurosensory retinal structure after anti-VEGF upload in age-related macular degeneration (AMD), by using spectral domain optical coherence tomography (SD-OCT). METHODS The retinal structure was observed by using SD-OCT in 61 patients, before and 1 month after the third ranibizumab injection (upload phase). The main focus of attention was a subjective determination of the amount and behavior of the numerous small, dense particles (SDPs) frequently observed within the outer and inner neurosensory layers in eyes with neovascular AMD. The Spearman rho correlation was used for statistical analysis. RESULTS In all eyes, various amounts of SDPs were seen within the neurosensory layer of the foveal and parafoveal area. In 54%, the amount of SDPs became significantly less after ranibizumab therapy (stable, 41%; higher, 5%). SDP reduction correlated positively with the reduction of retinal disease according to OCT (P = 0.000), with central foveal thickness (P = 0.040), and with the improvement in best corrected visual acuity (BCVA; P = 0.006). The baseline amount of SDPs also correlated positively with the increase in BCVA (P = 0.005). CONCLUSIONS The origin of the SDPs observable in SD-OCT is unknown, but they may represent migrating RPE cells or leukocytes, indicating a certain status of retinal inflammation. The amount of SDPs is substantially reduced after ranibizumab upload therapy and correlates positively with BCVA. Moreover, an initial large number of SDPs may indicate a higher grade of inflammation, but the presence of a high number enhances the effect of ranibizumab therapy. Thus, the amount of SDPs before treatment may be a predictive factor for the therapys outcome.

Association of macular pigment density with plasma ω-3 fatty acids: the PIMAVOSA study

PURPOSE To assess the correlation between macular pigment optical density and plasma levels of lutein, zeaxanthin, and fatty acids, especially omega-3 polyunsaturated fatty acids (PUFAs). METHODS The PIMAVOSA study is an observational study of 107 healthy volunteers, aged 20 to 60 years and born in southwest France, without histories of ocular disease. Macular pigment optical density (MPOD) was measured using the two-wavelength autofluorescence method with a modified scanning laser ophthalmoscope. Plasma measurements (lutein, zeaxanthin, and fatty acids) were performed from fasting blood samples collected on the day of the eye examination. RESULTS MPOD within 6° correlated with plasma levels of lutein and zeaxanthin (r = 0.35, P < 0.001, and r = 0.30, P < 0.005, respectively). MPOD also significantly correlated with total plasma omega-3 PUFAs (r = 0.22, P < 0.05). Among the different omega-3 PUFAs, docosapentaenoic acid (DPA) had the highest correlation with MPOD (r = 0.31, P < 0.001), whereas correlation with eicosapentaenoic acid (EPA) was moderate (r = 0.21, P < 0.05) and did not reach statistical significance for docosahexaenoic acid (r = 0.14, P = 0.14). CONCLUSIONS In the present study, macular pigment density was associated not only with plasma lutein and zeaxanthin but also with omega-3 long-chain PUFAs, particularly with EPA and DPA. Further studies will be needed to confirm these findings and to identify the underlying mechanisms.

Predictors of Short-Term Visual Outcome after Anti-VEGF Therapy of Macular Edema due to Central Retinal Vein Occlusion

PURPOSE The purpose of this study was to analyze predictive factors for best-corrected visual acuity (BCVA) after anti-VEGF treatment in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). METHODS This prospective study enrolled treatment-naive patients with ME secondary to CRVO. BCVA, ophthalmoscopy, fundus photography, and spectral domain optical coherence tomography (SD-OCT) imaging were performed. SD-OCT was analyzed for integrity of the external limiting membrane (ELM), photoreceptor inner segments (IS), and outer segments (OS). Patients were treated with intravitreal bevacizumab (1.25 mg) or ranibizumab (0.5 mg). BCVA outcome was analyzed 4 weeks after the first injection. RESULTS Sixty-two eyes of 62 patients (39 men, 23 women; mean age: 67 ±16 years) were included. In 55%, the ELM was intact. These eyes also showed intact photoreceptor IS/OS in horizontal and vertical single scans. Disturbed ELM was seen in 45% and was accompanied by focal disintegration of IS/OS. Four weeks after injection, 58% showed clinically relevant increases of BCVA (≥5 letters). Mean BCVA ranged from 20 to 86 letters. The mean BCVA increase was 18 ± 12 letters in eyes with intact ELM compared with 4 ± 10 letters with disturbed ELM (P < 0.001). CONCLUSIONS Depending on the integrity of the outer retinal layers, the authors observed rapid and clinically relevant improvement in BCVA after the first anti-VEGF injection. In the development of an optimal treatment regime, the indication for treatment and re-treatment should be based on functional and morphologic findings, such as the deterioration of outer retinal layers. Intact ELM in SD-OCT imaging is associated with better visual outcomes after intravitreal anti-VEGF treatment in patients with ME secondary to CRVO.