High-resolution optical coherence tomography of subpigment epithelial structures in patients with pigment epithelium detachment secondary to age-related macular degeneration.

BACKGROUND: The pathophysiology of pigment epithelial detachment (PED) secondary to age-related macular degeneration (AMD) is as yet incompletely understood and treatment remains challenging. Spectral domain optical coherence tomography (SD-OCT) allows for improved morphological characterisation of the space underneath the retinal pigment epithelium (RPE). OBJECTIVE: To investigate eyes with PED for structures underneath the detached RPE cell layer. METHODS: In a retrospective observational case study, SD-OCT scans of AMD-related PEDs were assessed for the presence of distinctive morphological features in the space between the detached RPE and inner Bruch's membrane. RESULTS: Structures present in the space between the detached RPE and Bruch's membrane were found in 14 of 90 eyes with AMD-related PED. Each of these eyes shows hyper-reflective material underneath the PED, presenting as highly reflective, multilayered, laminar structures, usually orientated parallel to Bruch's membrane. CONCLUSIONS: The findings indicate that SD-OCT may be useful for a more refined phenotypic stratification of AMD-associated PED. Further studies are warranted to explore the correlates on other imaging modalities, to investigate the composition of this material and to assess the potential prognostic relevance of this new finding.

Incidence of rhegmatogenous retinal detachments after intravitreal antivascular endothelial factor injections.

PURPOSE: To determine the incidence of rhegmatogenous retinal detachments (RD) after intravitreal injection in six high-volume centres. METHODS: A consecutive, interventional, multicenter case series measured the incidence of RD in patients receiving intravitreal anti-VEGF. A total of 35 942 intravitreal anti-VEGF injections (the number of the injections determined by review of injection log books over a 3 year period) were performed under sterile conditions with the patient in a supine position. Injections were given 3.5-4.0 mm behind the limbus in a tunnelled fashion. RESULTS: During 36 consecutive months, five RD were reported, between 2 and 6 days after the injection. Of the affected eyes, four were myopic -1.75 to -5.5 dpt. The incidence rate of rhegmatogenous RD was 0.013% (5/35 942) per injection. CONCLUSIONS: The incidence of RD in our community setting was very low (1 per 7188 injections). All RD occurred during the early postoperative period. The risks of RD can be minimized by a careful injection technique.

Incidence of damage to the crystalline lens during intravitreal injections.

PURPOSE: To report the incidence of traumatic lens injuries as a complication of intravitreal injection at 5 high-volume academic centers. METHODS: We determined in a retrospective, interventional, multicenter case series the consecutive number of the injections between January 5, 2006 and December 22, 2008 from the injection log books. All injections were performed under sterile conditions in a laying position, 3.5-4.0 mm behind the limbus in an oblique fashion. The main outcome measure was the incidence of lens damage. RESULTS: A total of 32,318 intravitreal injections were performed, and 3 cases of iatrogenic lens damage were reported during 36 consecutive months. All affected eyes were hyperopic. The overall incidence rate of lens injury was 0.006% (2/32,318) for intravitreal injections and 1 during a paracentesis 0.003 (1/32,318). The rate of phakic eyes determined was 67%, and thus, the incidence rate of lens damage in phakic eyes was 0.009% (2/21,653) (95% confidence interval, 0.00%-0.05%). CONCLUSIONS: Although there is no agreement regarding the proper intravitreal injection technique, the incidence of traumatic injuries to the crystalline lens was very low in a large series of injected patients in a community setting. The incidence compares favorably with that reported in clinical trials in which much more extensive preinjection preparation was mandated. A good preparation of the surgical incision with proper anesthesia and detailed information of the patient, as well as good anatomical skills of the treating physician, are mandatory to prevent this rare adverse event.

Choroidal detachment after an uneventful intravitreal injection.

PURPOSE: The purpose of this report was to describe a case of choroidal detachment after an uneventful intravitreal injection using a 30-gauge needle. METHODS: An 88-year-old patient with acute onset of neovascular age-related macular degeneration developed a choroidal detachment after an uneventful intravitreal injection in the infero-temporal aspect of the fundus. RESULTS: The patient described no symptoms related to the chorioretinal detachment. Additional intravitreal injections were required to treat an active subfoveal choroidal neovascularization. These injections were placed at the contralateral side in the supero-nasal quadrant. She was closely watched on a 2-week follow-up schedule. The choroidal detachment remained asymptomatic for the patient and resolved spontaneously, and the best corrected visual acuity improved from 0.2 to 0.63 during a 6-month follow-up. A mild hyperpigmentation remained at this location. CONCLUSION: Asymptomatic choroidal detachments may occur after intravitreal injection. Although treatment was not needed, additional injections should be avoided in the same quadrant until the detachment has resolved.

Tracking progression with spectral-domain optical coherence tomography in geographic atrophy caused by age-related macular degeneration.

PURPOSE: To investigate, with the use of spectral-domain optical coherence tomography (SD-OCT), microstructural alterations over time in eyes with progressive geographic atrophy (GA) due to age-related macular degeneration. METHODS: Forty-six eyes of 26 patients (median age, 77.9 years [interquartile range (IQR), 71.8-81.0]) with GA without evidence of active or previous neovascular disease at baseline were examined by simultaneous confocal scanning laser ophthalmoscopy (cSLO) and SD-OCT. Serial examinations with alignment of follow-up to baseline scans were performed over a median period of 12.2 months (IQR, 10.2-15.3). Longitudinal SD-OCT variations were evaluated, including quantification of retinal thickness (RT) change and lateral spread of GA (LSGA) at a temporal, nasal, inferior, and superior GA border-section in each eye. RESULTS: GA-enlargement was characterized by progressive loss of the outer hyperreflective SD-OCT bands and by thinning of the outer nuclear layer with subsequent approach of the outer plexiform layer toward Bruch's membrane. In the perilesional zone, various dynamic changes were recorded, including migration of hyperreflective material and changes in drusen height. At the borders, there was a median RT change of -14.09 microm/y (IQR -26.21 to -7.48 microm/y). The median LSGA was 106.90 microm/y (IQR, 55.44-161.70 microm/y). Both parameters showed only moderate intraocular agreement (RT change: intraclass correlation coefficient [ICC], 0.54; 95% CI, 0.39-0.67; LSGA: ICC, 0.49; 95% CI, 0.34-0.64) and no statistical significant difference for one location (RT change, P = 0.125; LSGA, P = 0.516; likelihood ratio test). CONCLUSIONS: Combined cSLO and SD-OCT imaging provides unprecedented insight into dynamic microstructural changes of GA enlargement that may help to better understand the pathogenesis of the disease. Quantitative progression data indicate local factors may exist that drive progression in junctional areas (ClinicalTrials.gov number, NCT00393692).

Clinical evaluation of simultaneous confocal scanning laser ophthalmoscopy imaging combined with high-resolution, spectral-domain optical coherence tomography.

PURPOSE: To evaluate the clinical relevance of a new diagnostic modality, simultaneous confocal scanning laser ophthalmoscopy (cSLO) and high-speed, high-resolution, spectral-domain optical coherence tomography (OCT), for the visualization of macular pathologies. METHODS: OCT images and simultaneous recording of fluorescein angiography, indocyanine green (ICG) angiography, infrared, and blue reflectance ('red-free') or fundus autofluorecence (FAF) images were obtained with a novel imaging device (Spectralis HRA + OCT; Heidelberg Engineering, Heidelberg, Germany). An optically pumped solid-state laser generated the excitation wavelength (488 nm) required for blue reflectance, FAF and fluorescein angiography images. For ICG angiography and infrared imaging, diode laser sources at 790 and 815 nm were used. For OCT, 40 000 A-scans per second were acquired with 7 µm axial and 14 µm lateral optical resolution. The B-scans covering a transversal range of 30° had a scan width up to 1.536 A-scans with a digital lateral resolution of 5 µm/pixel, a scan depth of 1.8 mm with 3.5 µm/pixel digital axial resolution and a scan rate of up to 48 B-scans/second. In addition, volume scans could be obtained at 15, 20 and 30° fields of view. An integrated eye tracking allowed for live averaging of cSLO images as well as OCT B-scans. RESULTS: Early, neovascular and atrophic age-related macular degeneration, macular telangiectasia, retinal arterial, branch vein occlusion and other pathologies were imaged, and cSLO and OCT frames correlated. Fluorescein and ICG angiographic phenomena recorded in cSLO images could be analysed accurately in corresponding OCT cross-sections. Abnormal FAF signals were correlated to alterations at the outer retinal/retinal pigment epithelial cell layer in high-resolution OCT scans. Three-dimensional OCT enabled comprehensive retinal coverage. The imaging software tracked eye movements accurately. Averaging of live B-scans enhanced image quality considerably. CONCLUSION: The combined cSLO/OCT system allowed for simultaneous recordings of topographic and tomographic images with accurate correlation between the confocal angiograms, FAF images as well as other imaging modes with the OCT scans. The instrument thus provides simultaneous multi-modal imaging of retinal pathologies and disease.

In vivo imaging of foveal sparing in geographic atrophy secondary to age-related macular degeneration.

PURPOSE: To investigate morphologic alterations in geographic atrophy caused by age-related macular degeneration (AMD) in the presence of foveal sparing using high-resolution in vivo imaging. METHODS: Simultaneous spectral domain optical coherence tomography (SD-OCT, 870 nm, 40,000 A-scans/s) and confocal scanning laser ophthalmoscopy (cSLO; fundus autofluorescence; excitation, 488 nm; emission, 500-700 nm) were performed in 18 eyes with geographic atrophy and foveal sparing using a combined instrument. Anatomic layers were evaluated, and retinal thickness in the fovea and the peripheral macula were measured and compared with those in controls of similar age. RESULTS: Fundus autofluorescence imaging showed an inhomogeneously reduced signal at the residual foveal island. SD-OCT scans disclosed mitigation of the foveal pit in the absence of extracellular fluid accumulation and an increased mean central retinal thickness of 248 +/- 28 microm compared with 225 +/- 12 microm in control eyes (P = 0.005). No difference in retinal thickness in the peripheral macula was observed (245 +/- 16 vs. 253 +/- 11 microm; P = 0.6). Subanalysis revealed marked appearance of swelling and widening of visible structures at the central outer nuclear layer (153 +/- 22 microm vs. 127 +/- 12 microm; P = 0.003). Below the external limiting membrane, a broad band of irregular high reflectivity was detected instead of the normal three separate reflective bands. CONCLUSIONS: Thickening at the foveal site may reflect a pre-apoptotic stage of neuronal cellular elements indicating imminent atrophy. Limited structure-function correlation found in our study suggests that future therapeutic intervention may be beneficial in only a subset of AMD patients with foveal sparing.

Abnormal macular pigment distribution in type 2 idiopathic macular telangiectasia.

PURPOSE: To determine the distribution of macular pigment in type 2 idiopathic macular telangiectasia (IMT). METHODS: Twenty-two eyes of 12 patients with type 2 IMT were examined by means of best-corrected visual acuity testing, fundus biomicroscopy, fundus photography, fluorescein angiography, and optical coherence tomography. Macular pigment optical density (MPOD) was assessed using a modified confocal scanning laser ophthalmoscope whereby MPOD was calculated from fundus autofluorescence images acquired at two different excitation wavelengths (488 and 514 nm). The results were verified with a method that provides density maps after digital subtraction of log fundus reflectance maps (four patients) and by means of heterochromatic flicker photometry (four patients). RESULTS: MOPD distribution showed an abnormal pattern for all patients with type 2 IMT. In correspondence to the late-phase hyperfluorescent areas shown by fluorescein angiography, MPOD was reduced in the macular area, while there was preserved MPOD at 5 degrees to 7 degrees eccentricity. CONCLUSIONS: The central depletion of macular pigment represents a novel phenotypic characteristic of type 2 IMT. Recording of macular pigment distribution may prove useful in the diagnosis of type 2 IMT and implicates an impaired trafficking or storage of lutein and zeaxanthin in the disease process.

High-resolution spectral domain-OCT imaging in geographic atrophy associated with age-related macular degeneration.

PURPOSE: To describe morphologic variations in outer retinal layers in eyes with atrophic age-related macular degeneration (AMD) using high-resolution, spectral-domain optical coherence tomography (SD-OCT). METHODS: SD-OCT scans were obtained with a combined confocal scanning laser ophthalmoscope (cSLO) and SD-OCT for simultaneous tomographic and topographic in vivo imaging. A total of 81 eyes of 56 patients (mean age, 77.8 +/- 7.4 years) with geographic atrophy (GA) were examined. Morphologic alterations were analyzed and classified in the perilesional zone, at the junction between GA and nonatrophic retina, and in the atrophic area itself. RESULTS: In the perilesional zone, distinct morphologic alterations included elevations of the outer retinal layers, thickening, and spikes of the outer hyperreflective band as well as clumps at different neurosensory retinal levels. At the junction, highly variable transitions of the outer retinal layers were present with different degrees of loss of the normal hyperreflective bands. Within the actual GA, hyperreflective clumps at different retinal levels, segmented plaques of the outer band and elevations with variable reflectivity were visualized. CONCLUSIONS: SD-OCT imaging in eyes with GA revealed a wide spectrum of morphologic alterations, both in the surrounding retinal tissue and in the atrophic area. These alterations may reflect different disease stages or, alternatively, heterogeneity on a cellular and molecular level. Longitudinal studies using in vivo SD-OCT imaging may allow evaluation of the relevance of these phenotypic changes as potential predictive markers for the progression of disease (i.e., enlargement rates of GA over time) and may be used for monitoring of future therapeutic interventions.

In vivo visualization of dendritic cells, macrophages, and microglial cells responding to laser-induced damage in the fundus of the eye.

PURPOSE: To study the in vivo response of mononuclear phagocytes (i.e., dendritic cells [DCs] and macrophages [MPhis]) in the posterior eye segment after laser-induced injury, and to gain a better understanding of the role of these cells in inflammatory eye disease. METHODS: CX(3)CR1(GFP/+) knockin mice were used, in which DCs, MPhis, and microglia cells (microGCs) are constitutively fluorescent. These reporter mice were examined by a confocal scanning laser ophthalmoscope (cSLO) after argon laser coagulation. cSLO was complemented by fluorescence microscopy of retinal flatmounts and eye cryosections, to study cell morphology and location, and by multicolor flow cytometry, to determine the number and identity of the fluorescent cells. RESULTS: The retina of healthy reporter mice featured abundant fluorescent microGCs. After laser injury to the fundus, these cells accumulated and migrated laterally toward injury after 60 minutes. Distinctly shaped fluorescent cells accumulated within laser spots and were identified by flow cytometry and immunofluorescence microscopy as DCs and MPhis in the retina and choroid. The DCs rapidly disappeared from the retina, whereas the MPhis stayed longer. Choroidal infiltrates were detectable even 35 days after laser injury, in particular in larger spots resulting from higher laser intensity. In addition, nonfluorescent granulocytes were detected in the choroid. CONCLUSIONS: The synergistic use of ophthalmoscopy, flow cytometry, and immunofluorescence microscopy allows detailed dissection of the in vivo response of mononuclear phagocytes to laser injury of the fundus. The number of microGCs increased in the retina. DCs and MPhis were present in the retina and choroid infiltrate. MPhis and granulocytes persisted in the choroid infiltrate longer than previously thought.

Combined treatment of acute subretinal haemorrhages with intravitreal recombined tissue plasminogen activator, expansile gas and bevacizumab: a retrospective pilot study.

PURPOSE: To assess the effectiveness of consecutive intravitreal injections of recombined tissue plasminogen activator (rtPA), expansile gas and bevacizumab in eyes with acute subretinal haemorrhage (SRH). METHODS: A retrospective, non-randomized consecutive case series included 19 eyes in 19 patients with SRH related to exudative age-related macular degeneration (AMD). The initial size of the subfoveal SRH was 1-3 disc diameters. Each patient received a triple procedure using 0.05 ml rtPA (50 microg), 0.3 ml of sulphur hexafluoride (SF6) gas and 0.05 ml bevacizumab (1.25 mg). Lesion size, location of the SRH and early treatment in diabetic retinopathy study (ETDRS) visual acuity were evaluated pretreatment as well as 1 and 3 months after the procedure. RESULTS: At the initial presentation, the patients' mean age was 77 years (range 63-88 years) and the mean duration of symptoms was 9.3 days (range 4-12 days). The mean visual acuity pretreatment (20/133) improved significantly to 20/86 at 1 month and to 20/74 at 3 months. The mean ETDRS visual acuity improved from baseline by 2.1 lines at 1 month (Wilcoxon ranks test; P < 0.005) and 3.7 lines at 3 months after treatment (Wilcoxon ranks test; P < 0.005). None of our patients had reading visual acuity prior to treatment, with visual acuity below 0.3. One month after the triple procedure, 25% of our patients had reading visual acuity (> or = 0.4); at 3 months, the figure was 35%. A successful inferior displacement of the SRH was achieved in 17/19 eyes. Eyes with elevated intraocular pressure were treated immediately by a corneal paracentesis. CONCLUSION: The intravitreal application of rtPA, gas and bevacizumab appears to be beneficial and well tolerated in the treatment of SRH in the short term. The triple approach seems a logical alternative to the current combined dual approach in limiting the progression of the underlying disease and achieving better visual outcome. Further randomized evaluations are warranted.

Correlation of macular function with retinal thickness in nonproliferative type 2 idiopathic macular telangiectasia.

PURPOSE: To correlate macular thickness determined by optical coherence tomography (OCT) with light increment sensitivity and visual acuity in patients with type 2 idiopathic macular telangiectasia (IMT). DESIGN: Prospective, cross-sectional study. METHODS: Fifty-one eyes of 30 patients with type 2 IMT were investigated. Functional assessment included best-corrected visual acuity and fundus-related microperimetry (MP1; Nidek Technologies, Padova, Italy). Retinal thickness was analyzed quantitatively by OCT3 (Carl Zeiss Meditec, Jena, Germany). The main outcome measure was the correlation of light sensitivity and visual acuity with retinal thickness. RESULTS: Mean central retinal thickness was reduced compared with that of normal eyes. There was no significant correlation between central foveal thickness and foveal light sensitivity or visual acuity, respectively. Also, there was no significant correlation between mean retinal thickness temporal to the fovea and the lowest light sensitivity within that area. However, central light sensitivity in eyes with normal central foveal thickness was lower than in eyes with subnormal central foveal thickness (P = .032); this was also true for the lowest light sensitivity found temporal to the fovea (P = .025). Mean visual acuity was 20/40 and did not show significant differences in the two thickness groups. CONCLUSIONS: A subnormal foveal thickness in type 2 IMT may be associated with better macular function as assessed by microperimetry. It is hypothesized that in type 2 IMT, both a primary neurosensory thinning and a low-grade macular edema can be involved. The coincidence may result in normal retinal thickness but decreased retinal function.

Combined intravitreal bevacizumab and photodynamic therapy for neovascular age-related macular degeneration.

BACKGROUND: Our aim was to evaluate the short-term safety and efficacy of combined photodynamic therapy (PDT) with verteporfin and intravitreal bevacizumab in neovascular age-related macular degeneration (AMD). METHODS: A prospective non-randomized interventional case series of 30 eyes of 30 patients with choroidal neovascularization (CNV) caused by AMD was studied. All patients were treated with PDT followed by an intravitreal injection of bevacizumab (1.5 mg) on the same day. Ophthalmic evaluations included determination of best-corrected visual acuity by using ETDRS charts. CNV lesion characteristics were determined by fluorescein angiography, and retinal morphology by optical coherence tomography. Review examinations were performed 1, 4, and 12 weeks following treatment. RESULTS: The median ETDRS letter scores increased by 3 letters after 4 weeks and 4.3 letters after 12 weeks. Median central retinal thickness decreased from the baseline by 145 microm (week 1), 205 microm (week 4), and 171 microm (week 12), respectively (P < 0.0001, for all comparisons). One patient experienced a transient moderate vision loss after 4 weeks post treatment. Leakage on fluorescein angiography was resolved in all patients at week 12. No significant ocular or systemic side-effects were observed. CONCLUSIONS: Short-term results suggest that a single PDT in combination with intravitreal bevacizumab is safe and associated with stabilization of visual acuity and decrease of intraretinal and subretinal fluid accumulation in the macula. Further evaluation of this treatment strategy for neovascular AMD appears warranted.

Microperimetric assessment of patients with type 2 idiopathic macular telangiectasia.

PURPOSE: To assess changes of the light increment sensitivity (LIS) of the macular area in patients with type 2 idiopathic macular telangiectasia (IMT). METHODS: Fifty-eight eyes of 30 patients were examined in a cross-sectional study. All eyes were assigned to group A (early disease stages) or group B (late disease stages with retinal pigment clumping or vascular membranes). Investigation of visual function included visual acuity and fundus-related microperimetry. RESULTS: Thirty-seven and 16 eyes were assigned to group A and group B, respectively. Temporal to the fovea, each eye of group B had an absolute scotoma. Topographically, the areas with reduced LIS correlated well with the angiographically hyperfluorescent areas or retinal pigmentations and showed a sharp demarcation from areas with normal LIS. However, within areas with angiographic alterations, at least some test locations exhibited preserved LIS in group B eyes; in 51% of group A eyes, none of those test locations showed abnormal LIS. Group A eyes that showed marked LIS reduction revealed common abnormalities: either hyporeflective spaces between the neurosensory retina and the retinal pigment epithelium in OCT imaging or atrophic areas, both topographically related to the scotoma. Visual acuity was correlated with foveal LIS but not with the LIS temporal to the fovea. CONCLUSIONS: Long-standing morphologic macular alterations from type 2 IMT are associated with topographically related functional impairment. Eyes with profound parafoveal scotomas can exhibit relatively preserved visual acuity. Therefore, testing for retinal light sensitivity should be included as an additional outcome measure for future interventional studies.