Inter-Device Comparison of Blue-Light Autofluorescence in Optic Disc Drusen.

PURPOSE: Monochromatic blue-light fundus autofluorescence has proven to be particularly useful for the detection of optic disc drusen (ODD). The aim of this study was to investigate how accurately novel confocal scanners can detect ODD by means of color fundus and autofluorescence images. METHODS: Images were taken in 20 consecutive patients' eyes with funduscopically visible ODD using the TrueColor Eidon AF (60 × 55°) and the spectral domain Spectralis HRA+OCT (30 × 30°). The features of ODD, including localization, extent, and intensity patterns of autofluorescence were compared and correlated with retinal nerve fiber layer (RNFL) thickness in OCT and perimetry findings. RESULTS: Mean patient age was 46 ± 6 years (6 females, 4 males). The TrueColor Eidon AF enabled accurate localization and extent estimation of the drusen area. Drusen presented as a homogeneous signal. The predilection site of ODD, which was nasally pronounced in >80% of cases, was associated with thinning of the RNFL and corresponding visual field defects. CONCLUSION: The TrueColor Eidon AF allows reliable detection of superficial ODD in nondilated eyes. Extended observational studies are needed to determine the value of this noninvasive, nonmydriatic procedure in terms of follow-up and progression analyses of ODD.

Directional Kinetics of Geographic Atrophy Progression in Age-Related Macular Degeneration with Foveal Sparing.

PURPOSE: To describe the directional kinetics of the spread of geographic atrophy (GA) spread in eyes with age-related macular degeneration and foveal sparing. DESIGN: Prospective, noninterventional natural history study: Fundus Autofluorescence Imaging in Age-Related Macular Degeneration (FAM; clinicaltrials.gov identifier, NCT00393692). SUBJECTS: Participants of the FAM study exhibiting foveal sparing of GA. METHODS: Eyes were examined longitudinally with fundus autofluorescence (FAF; excitation wavelength, 488 nm; emission wavelength, >500 nm) and near infrared (NIR) reflectance imaging (Spectralis HRA+OCT or HRA2; Heidelberg Engineering, Heidelberg, Germany). Areas of foveal sparing and GA were measured by 2 independent readers using a semiautomated software tool that allows for combined NIR reflectance and FAF image grading (RegionFinder; Heidelberg Engineering). A linear mixed effect model was used to model GA kinetics over time. MAIN OUTCOME MEASURE: Change of GA lesion size over time (central vs. peripheral progression). RESULTS: A total of 47 eyes of 36 patients (mean age, 73.8±7.5 years) met the inclusion criteria. Mean follow-up time was 25.2±16.9 months (range, 5.9-74.6 months). Interreader agreement for measurements of GA and foveal-sparing size were 0.995 and 0.946, respectively. Mean area progression of GA toward the periphery was 2.27±0.22 mm(2)/year and 0.25±0.03 mm(2)/year toward the center. Analysis of square root-transformed data revealed a 2.8-fold faster atrophy progression toward the periphery than toward the fovea. Faster atrophy progression toward the fovea correlated with faster progression toward the periphery in presence of marked interindividual differences. CONCLUSIONS: The results demonstrate a significantly faster centrifugal than centripetal GA spread in eyes with GA and foveal sparing. Although the underlying pathomechanisms for differential GA progression remain unknown, local factors may be operative that protect the foveal retina-retinal pigment epithelial complex. Quantification of directional spread characteristics and modeling may be useful in the design of interventional clinical trials aiming to prolong foveal survival in eyes with GA.

Treatment of choroidal neovascularization due to angioid streaks: a comprehensive review.

PURPOSE: To evaluate different therapies for choroidal neovascularization (CNV) due to angioid streaks (AS). METHODS: Studies were identified by a systematic literature search and were included in the analysis based on predefined criteria. Primary outcome measure was change in best-corrected visual acuity (BCVA). RESULTS: Fifty-four relevant studies were identified and included mostly uncontrolled case series. No randomized controlled trials were available. Treatment with vascular endothelial growth factor inhibitors improved or stabilized BCVA in all case series. Photodynamic therapy slowed down disease progression with stabilization or decrease of BCVA. Individual BCVA and follow-up data for each treated eye were reported in >160 cases for both treatments, vascular endothelial growth factor inhibitors and photodynamic therapy. In a pooled analysis of those studies, the difference of mean change in BCVA between both treatment groups was estimated as approximately 6 lines (0.59 logMAR [95% confidence interval, 0.38-0.8; P < 0.0001]). A better baseline BCVA was associated with a better BCVA outcome (P < 0.0001). Laser photocoagulation yielded comparable results as photodynamic therapy but application was mostly restricted to extrafoveal lesions, was complicated by frequent recurrences, and led to more retinal damage with subsequent absolute scotomas. Combination therapies seem to be not superior to monotherapy. CONCLUSION: Intravitreal vascular endothelial growth factor inhibitors are currently the most effective treatment of CNV due to angioid streaks.

Release and velocity of micronized dexamethasone implants with an intravitreal drug delivery system: kinematic analysis with a high-speed camera.

PURPOSE: Ozurdex, a novel dexamethasone (DEX) implant, is released by a drug delivery system into the vitreous cavity. We analyzed the mechanical release aperture of the novel applicator, obtained real-time recordings using a high-speed camera system and performed kinematic analysis of the DEX application. DESIGN: Experimental study. METHODS: : The application of intravitreal DEX implants (6 mm length, 0.46 mm diameter; 700 µg DEX mass, 0.0012 g total implant mass) was recorded by a high-speed camera (500 frames per second) in water (Group A: n = 7) or vitreous (Group B: n = 7) filled tanks. Kinematic analysis calculated the initial muzzle velocity as well as the impact on the retinal surface at approximately 15 mm of the injected drug delivery system implant in both groups. A series of drug delivery system implant positions was obtained and graphically plotted over time. RESULTS: High-speed real-time recordings revealed that the entire movement of the DEX implant lasted between 28 milliseconds and 55 milliseconds in Group A and 1 millisecond and 7 milliseconds in Group B. The implants moved with a mean muzzle velocity of 820 ± 350 mm/s (±SD, range, 326-1,349 mm/s) in Group A and 817 ± 307 mm/s (±SD, range, 373-1,185 mm/s) in Group B. In both groups, the implant gradually decelerated because of drag force. With greater distances, the velocity of the DEX implant decreased exponentially to a complete stop at 13.9 mm to 24.7 mm in Group A and at 6.4 mm to 8.0 mm in Group B. Five DEX implants in Group A reached a total distance of more than 15 mm, and their calculated mean velocity at a retinal impact of 15 mm was 408 ± 145 mm/s (±SD, range, 322-667 mm/s), and the consecutive normalized energy was 0.55 ± 0.44 J/m (±SD). In Group B, none of the DEX implants reached a total distance of 6 mm or more. An accidental application at an angle of 30 grade and consecutively reduced distance of approximately 6 mm may result in a mean velocity of 844 and mean normalized energy of 0.15 J/m (SD ± 0.47) in a water-filled eye. CONCLUSION: The muzzle velocity of DEX implants is approximately 0.8 m/s and decreases exponentially over distance. The drag over time in vitreous is faster than in water. The calculated retinal impact energy does not reach reported damage levels for direct foreign bodies or other projectiles.

Imaging geographic atrophy in age-related macular degeneration.

Advances in retinal imaging technology have largely contributed to the understanding of the natural history, prognostic markers and disease mechanisms of geographic atrophy (GA) due to age-related macular degeneration. There is still no therapy available to halt or slow the disease process. In order to evaluate potential therapeutic effects in interventional trials, there is a need for precise quantification of the GA progression rate. Fundus autofluorescence imaging allows for accurate identification and segmentation of atrophic areas and currently represents the gold standard for evaluating progressive GA enlargement. By means of high-resolution spectral-domain optical coherence tomography, distinct microstructural alterations related to GA can be visualized.

Combined confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography imaging of reticular drusen associated with age-related macular degeneration.

PURPOSE: To determine microstructural retinal alterations associated with reticular drusen in patients with age-related macular degeneration (AMD) using high-resolution in vivo imaging techniques. DESIGN: Retrospective case series. PARTICIPANTS: A total of 116 eyes of 78 AMD patients with reticular drusen were examined. METHODS: Simultaneous spectral-domain optical coherence tomography (SD OCT; 870 nm, 40,000 A-scans/sec) and near-infrared confocal scanning laser ophthalmoscopy (cSLO; 830 nm) were performed using a combined imaging instrument (Spectralis HRA+OCT, Heidelberg Engineering, Heidelberg, Germany). Individual anatomic layers in SD OCT were evaluated and correlated to en face cSLO fundus imaging. MAIN OUTCOME MEASURES: Description of corresponding structural changes in areas of reticular drusen. RESULTS: Reticular drusen appeared as an interlacing network of round or oval irregularities by near-infrared cSLO reflectance imaging. On SD OCT, reticular drusen corresponded to marked changes at a level anterior to the retinal pigment epithelium (RPE) and Bruch's membrane complex to the interface of inner and outer photoreceptor segment layer (IPRL). Individual reticular drusen correlated to focal elevations of the IPRL, accumulation of highly reflective material below the IPRL, and an increased distance between the IPRL and RPE. CONCLUSIONS: The findings indicate that the morphologic substrate of reticular drusen is the accumulation of highly reflective material within outer retinal layers anterior to the RPE. This is in contrast to previous assumptions pointing toward a localization of abnormal material at the level of the inner choroid. Although the origin of the material is unknown, the results may indicate a role for primary abnormalities in the neurosensory retina. Because reticular drusen represent high-risk markers for the progression of AMD, their ready identification is relevant both for natural history studies as well as for interventional trials.

ORCA study: real-world versus reading centre assessment of disease activity of neovascular age-related macular degeneration (nAMD).

BACKGROUND/AIMS: The prospective, non-interventional ORCA module of the OCEAN study (Observation of Treatment Patterns with Lucentis in Approved Indications) evaluated the qualiy of spectral domain-optical coherence tomography (SD-OCT) image interpretation and treatment decisions by clinicians in Germany and the impact on visual outcomes over 24 months in patients with neovascular age-related macular degeneration (nAMD). METHODS: 2286 SD-OCT scans of 205 eyes were independently evaluated by clinicians and reading centres (RCs) regarding signs of choroidal neovascularisation (CNV) activity, including presence of intraretinal fluid, subretinal fluid, and/or increase in pigment epithelial detachments. Agreement between clinicians and RCs was calculated. Treatment decisions by clinicians and the impact on treatment outcomes were evaluated. RESULTS: CNV activity was detected by RCs on 1578 scans (69.0%) and by clinicians on 1392 scans (60.9%), with agreement in 74.9% of cases. Of the 1578 scans with RC detected CNV activity, anti-vascular endothelial growth factor injections were performed by clinicians in only 35.5% (560/1578). In 19.7% of cases (311/1578), lack of treatment was justified by patients request, termination criteria or chronic cystoid spaces without other signs for CNV activity. In 44.8% of cases (707/1578) with RC detected CNV activity, clinicians claimed no treatment was necessary despite having correctly detected CNV activity in about 2/3 of these cases. In 34% of cases with presumed undertreatment, visual acuity declined in the following visit. CONCLUSION: Although broad agreement on CNV activity parameters was observed between clinicians and RCs, correct identification of CNV activity did not always lead to the initiation of (re-)treatment. To preserve vision over time, correct interpretation of SD-OCT scans and careful retreatment decisions are required. TRIAL REGISTRATION NUMBER: NCT02194803.

[Baseline diagnostics and initial treatment decision for anti-vascular endothelial growth factor treatment in retinal diseases : Comparison between results by study physician and reading centers (ORCA/OCEAN study)]. / Initiale Diagnostik und Indikationsstellung zur Anti-Vascular-Endothelial Growth-Factor-Therapie bei Netzhauterkrankungen : Vergleich der Befundung durch Studienarzt versus Reading Center (ORCA/OCEAN-Studie).

BACKGROUND: The ORCA module of the non-interventional OCEAN study investigated the use of retinal imaging diagnostics in the clinical treatment of patients undergoing vascular endothelial growth factor (VEGF) inhibitor treatment as part of routine clinical care. This article analyzes the agreement between the diagnosis documented by the treating ophthalmologist and the evaluation of reading centers at baseline as well as the effect on the response to treatment during the course. METHODS: A total of 396 patients (age 75.4 years) were enrolled in which ranibizumab treatment was indicated by the treating ophthalmologist due to either diabetic macular edema (DME), neovascular age-related macular degeneration (nvAMD) or retinal venous occlusion (RVO). Over a period of 24 months, patient and examination data, treatments and interpretation of retinal imaging data by the treating ophthalmologist were systematically recorded. Furthermore, retinal imaging data were also evaluated by three reading centers. RESULTS: In 338 out of 396 (85.4%) study eyes, the baseline diagnosis of the treating ophthalmologist was confirmed by the reading centers (DME 87.5%, nvAMD 82.3%, RVO 94.9%). In 17 of the remaining 58 eyes with a discrepant diagnosis, there was at least a consensus with respect to the indications for VEGF inhibitor therapy. The differential diagnoses included a variety of different retinal diseases. During follow-up of up to 3 months, eyes with a consistent diagnosis showed a clear increase in visual acuity (6.4 versus 2.7 letters, p = 0.05) and greater decrease in central retinal thickness (-112.3 versus -24.4 µm, p < 0.0001). DISCUSSION: The initial treatment decision for anti-VEGF therapy with consideration of the differential diagnoses can be challenging. Accurate evaluation of the clinical and imaging findings along with appropriate expertise appear to be important. The observation of superior initial response in eyes with a consensus of the diagnosis at baseline underlines the relevance of an adequate initial assessment for a successful treatment outcome.

Undilated versus dilated monoscopic smartphone-based fundus photography for optic nerve head evaluation.

Smartphone-based fundus photography (SBFP) allows for a cheap and mobile fundus examination with the potential to revolutionize eye care especially in low income settings. The purpose of this study was to assess the impact of pupil dilation on image quality in optic nerve head (ONH) imaging and vertical cup-to-disc ratio (vCDR) evaluation with SBFP. Eyes with glaucoma or suspected to have glaucoma were imaged with conventional digital fundus photography (CFP) and SBFP undilated and following dilation, all monoscopically. SBFP was possible in 74% of eyes without dilation and in 98% following dilation. Better image quality on SBFP was achieved with dilation and complete visualization of the optic disc rim was possible in 46% of images without dilation and on 94% of images with dilation. VCDR measurements on images obtained following dilation highly correlated with measurements on CFP (coefficient of correlation r = 0.91, p < 0.001), whereas vCDR on images obtained without dilation correlated less well with CFP (r = 0.70, p < 0.001). SBFP for ONH evaluation is promising, however dilation appears mandatory to achieve results comparable to optic disc evaluation on CFP. ONH imaging with smartphones without dilation might bear the risk of underestimating the CDR and hence overlooking patients at risk for glaucoma.

Visual field indices and patterns of visual field deficits in mesopic and dark-adapted two-colour fundus-controlled perimetry in macular diseases.

BACKGROUND/AIMS: To analyse the retest reliability of visual field indices and to describe patterns of visual field deficits in mesopic and dark-adapted two-colour fundus-controlled perimetry (FCP) in macular diseases. METHODS: Seventy-seven eyes (30 eyes with macular diseases and 47 normal eyes) underwent duplicate mesopic and dark-adapted two-colour FCP (Scotopic Macular Integrity Assessment, CenterVue). Non-weighted (mean defect, loss variance), variability-weighted (mean deviation, pattern standard deviation (PSD)) and graphical (cumulative defect (Bebie) curves) indices were computed. Reproducibility (coefficient of repeatability, CoR) of these indices was assessed. Cluster analysis was carried out to identify patterns of visual field deficits. RESULTS: The intrasession reproducibility was lower for the mean defect as compared with the mean deviation (CoR (dB) 2.67 vs 2.57 for mesopic, 1.71 vs 1.45 for dark-adapted cyan, 1.94 vs 1.87 for dark-adapted red testing) and lower for the square-root loss variance as compared with the PSD (CoR (dB) 1.48 vs 1.34, 0.77 vs 0.65, 1.23 vs 1.03). Hierarchical cluster analysis of the indices disclosed six patterns of visual field deficits (approximately unbiased P value>0.95) with varying degrees of global versus focal defect and rod versus cone dysfunction. These were also reflected by the cumulative defect curves. CONCLUSION: FCP with mesopic and dark-adapted two-colour testing allows for reproducible assessment of different types of retinal sensitivity, whereby mean deviation and PSD exhibited the better retest reliability of the tested indices. Distinct patterns of retinal dysfunction can be identified using this setup, reflecting variable degrees of rod and cone dysfunction in different macular diseases. Dark-adapted two-colour FCP provides additional diagnostic information and allows for refined structure-function correlation in macular diseases.

Choroidal thickness in geographic atrophy secondary to age-related macular degeneration.

PURPOSE: To analyze choroidal thickness (CT) in eyes with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). METHODS: A total of 72 eyes of 72 patients (mean age, 75.97 ± 7.09 years) with GA and 37 eyes of 37 healthy controls (73.89 ± 6.19 years) were examined by confocal scanning laser ophthalmoscopy and enhanced depth imaging (EDI) spectral-domain optical coherence tomography. Choroidal thickness was measured at 25 defined points in horizontal and vertical scans. Geographic atrophy size was determined in fundus autofluorescence (FAF) images and GA subtypes were classified based on abnormal FAF in the perilesional zone. RESULTS: In GA, subfoveal CT (fCT) was significantly thinner compared to controls (173.03 ± 90.22 vs. 253.95 ± 69.19 µm, P < 0.001). Analysis of averaged measurements of all 25 points obtained per patient (mCT) revealed similar results (162.07 ± 76.26 vs. 228.00 ± 66.24 µm, P < 0.001). Spatial differences in CT between both groups were largest superior to the fovea. Addressing "diffuse-trickling" (n = 15) and "non-diffuse-trickling" (n = 57) GA independently, fCT was 114.67 ± 43.32 and 188.39 ± 93.26 µm, respectively (P = 0.002), with both groups being significantly thinner than controls (P < 0.001 for "diffuse-trickling" and P < 0.001 for "?non-diffuse-trickling"). Similar results were obtained for mCT, which was 110.21 ± 29.66 µm in "diffuse-trickling," 175.72 ± 79.02 µm in "?non-diffuse-trickling" and 228.00 ± 66.24 µm in controls. Differences were significant with P = 0.002 between both GA groups and P ≤ 0.001 toward controls for each GA group. CONCLUSIONS: The results indicate that the choroid in eyes with GA is thinner compared to normal eyes of similar age. Hereby, the extent of thinning is most pronounced in a specific subtype of GA identified by FAF imaging ("diffuse trickling"). Such GA subtype-related differences in choroidal thickness may reflect heterogeneity in the pathogenesis of disease. (ClinicalTrials.gov number, NCT02051998.).

Penetration force, geometry, and cutting profile of the novel and old Ozurdex needle: the MONO study.

PURPOSE: To investigate the geometry, penetration force, and cutting profile of the novel and old needle of the drug delivery system (DDS) for Ozurdex injections in a standardized laboratory setting. METHODS: In this experimental study, the normative geometrical data of the DDS needle were systematically analyzed according to nomenclature DIN 13097 (ISO 7864) and ISO 9626. The force to penetrate a standardized 0.4-mm-thick polyurethane foil was measured by a penetrometer, when the needle was piercing, cutting, and sliding through the foil and plotted as a load-displacement diagram. Magnified images of the consecutive cut were taken after the entire penetration through the foil. RESULTS: In this experimental study, the mean point length was equal to 3.34 mm (3.28-3.36 mm) for the old DDS needle versus 3.33 mm (3.30-3.36 mm) for the new DDS needle. The secondary bevel length was 1.64 mm (1.42-1.73 mm) for the new and 1.66 mm (1.62-1.69 mm) for the old needle. The primary angle was 9.2° (9.0°-9.5°) for the old and 8.9° (8.5°-9.0°) for the new needle, respectively. The secondary bevel angle was 117.2° (116°-118°) for the old and 111.4° (110°-113°) for the new needle. The mean penetration force of the old DDS needles was significantly higher at all phases of the penetration experiment: The mean piercing force was 0.7 Newton (N) with the old and 0.47 N with the new DDS needle. The mean cutting force was remarkable higher with 1.1 N for the old DDS needle versus 0.78 N for the new DDS needle. The dilatation phase was not statistically significant between 0.94 and 0.99 N in both DDS needles. The friction phase was maintained at significantly higher levels with the old DDS needle of 0.47 N, whereas it returned to the lowest measurements of 0.11 N with the new DDS needle. Both DDS systems induced a characteristic chevron-shaped incision. CONCLUSION: A comparison of the old and new DDS needles demonstrated a reduced penetration force with the modified new DDS needle, which may help to achieve a smooth penetration through the human sclera.

Choroidal changes associated with Bruch membrane pathology in pseudoxanthoma elasticum.

PURPOSE: To investigate the impact of Bruch membrane pathology on the choroid in pseudoxanthoma elasticum (PXE). DESIGN: Monocenter cross-sectional prospective case series. METHODS: The study included 61 eyes of 51 patients with PXE and 54 eyes of 54 normal subjects. The diagnosis of PXE was based on skin biopsy, genetic analysis or both. Eyes with PXE were subdivided into 3 groups: eyes without choroidal neovascularization (CNV) or chorioretinal atrophy (Group 1); eyes with active or fibrotic CNV (Group 2); and eyes with chorioretinal atrophy only (Group 3). Choroidal thickness was measured using enhanced-depth imaging optical coherence tomography (EDI-OCT). RESULTS: Compared to controls (331 µm ± 24; mean ± 95% CI), mean subfoveal choroidal thickness in eyes of patients with PXE was significantly reduced within all 3 groups (Group 1: 243 µm ± 29; Group 2: 184 µm ± 28; Group 3: 104 µm ± 28; P < 0.001). Associated structural changes included apparent loss of small choroidal vessels. The difference of PXE compared to control eyes was largest close to the optic disc and approximated the level of controls toward the periphery. Within the PXE subgroups, eyes without CNV or chorioretinal atrophy (Group 1) showed the least reduction of choroidal thickness, while it was most pronounced in Group 3. CONCLUSIONS: The results indicate that changes of Bruch membrane can be associated with choroidal alterations, which are most pronounced in the presence of advanced disease. A role of Bruch membrane in choroidal homeostasis may reflect a possible contribution of Bruch membrane alterations to CNV and geographic atrophy development in age-related macular degeneration.

Effects of combination therapy with verteporfin photodynamic therapy and ranibizumab in patients with age-related macular degeneration.

PURPOSE: This open-label, prospective, small-scale study investigated the benefits of same-day verteporfin and intravitreal ranibizumab in patients with predominantly classic, minimally classic or occult subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration. METHODS: Patients received verteporfin at baseline and at month 3, if leakage persisted. Ranibizumab (0.5 mg) was given at baseline and months 1, 2 and 3, and thereafter at monthly intervals if required. Same-day ranibizumab was given ≥ 1 hr after verteporfin. RESULTS: Fifteen patients [11 male, four female; mean age 75.5 years (range 54-94 years)] were treated. At day 360, mean visual acuity (VA) had improved by 10.9 letters. An increase of ≥ 15 and ≥ 30 letters (i.e. ≥ 3 and ≥ 6 lines) was observed in seven (47%) patients and one patient (7%), respectively. Mean central retinal thickness (CRT) decreased by 85 µm. At days 7, 14 and 30, CNV perfusion was absent in 14/15 patients. Mean lesion area had reduced from baseline by 23.1% at day 120, 25.5% at day 180 and 23.6% at day 360. There were no visual safety concerns and intraocular pressures remained normal. Only two serious adverse events were recorded over the 12-month period, and neither was considered to be related to treatment. CONCLUSION: Same-day verteporfin plus ranibizumab improved VA, reduced CRT, prevented CNV perfusion and reduced lesion area safely over 12 months. Further investigation is warranted to confirm whether this combination improves long-term vision and reduces the need for retreatment.

Fundus autofluorescence and spectral-domain optical coherence tomography characteristics in a rapidly progressing form of geographic atrophy.

PURPOSE: To further characterize a previously described phenotypic variant of geographic atrophy (GA) associated with rapid progression and a diffuse-trickling appearance on fundus autofluorescence (FAF). METHODS: Thirty-six patients (60 eyes; 72.2% women; mean age, 69.4 ± 10.7 years) with this distinct phenotype were examined by simultaneous confocal scanning laser ophthalmoscopy (cSLO) and spectral-domain optical coherence tomography (SD-OCT) imaging. Images were qualitatively and quantitatively analyzed and compared with 60 eyes (38 patients) with non diffuse-trickling GA. RESULTS: The atrophic area in the diffuse-trickling phenotype showed a grayish FAF signal and characteristic coalescent lobular configuration at the lesion boundaries. SD-OCT revealed a marked splitting of band 4 (the presumptive retinal pigment epithelium (RPE)/Bruch's membrane (BM) complex) in all 240 analyzed border sections of diffuse-trickling GA eyes (four borders/eye) with a mean distance between the inner and outer parts of band 4 of 23.2 ± 7.5 µm. This finding was present in only 13.8% (33/240) of analyzed border sections in non diffuse-trickling GA. CONCLUSIONS: Patients with the rapidly progressing diffuse-trickling GA phenotype exhibited a characteristic marked separation within the RPE/BM complex on SD-OCT-imaging. The presumed histopathologic correlates are basal laminar deposits. Such deposits may promote RPE cell death and, thus, contribute to rapid GA progression. The persistence of these deposits within the atrophic lesion may account for the distinct grayish FAF appearance, which differs from the markedly reduced signal in other forms of GA. Identification of such alterations based on FAF and SD-OCT imaging may be helpful in future interventional trials directed toward slowing GA progression. (ClinicalTrials.gov number, NCT00393692.).

Semiautomated image processing method for identification and quantification of geographic atrophy in age-related macular degeneration.

PURPOSE: To determine intraobserver and interobserver longitudinal measurement variability of novel semiautomated software for quantification of age-related macular degeneration-associated geographic atrophy (GA) based on confocal scanning laser ophthalmoscopy fundus autofluorescence (FAF) imaging. METHODS: Three-field FAF (excitation 488 nm, emission 500-700 nm), near-infrared reflectance (820 nm), and blue reflectance (488 nm) images of 30 GA subjects were recorded according to a standardized protocol at baseline after 6 and 12 months. At all visits, the GA area was analyzed on central FAF images by seven independent readers using semiautomated software. The software allows direct export of FAF images from the database and semiautomated detection of atrophic areas by shadow correction, vessel detection, and selection of seed points. RESULTS: The mean size of atrophy at baseline and the mean progression rate were 5.96 mm² (range, 1.80-15.87) and 1.25 mm²/year (0.42-2.93), respectively. Mean difference of interobserver agreement (Bland-Altman statistics) ranged from -0.25 to 0.30 mm² for the baseline visit and from -0.14 to 0.11 mm²/year for the atrophy progression rate. Corresponding reflectance images were helpful for lesion boundary discrimination, particularly for evaluation of foveal GA involvement and when image quality was poor. CONCLUSIONS: The new image processing software offers an accurate, reproducible, and time-efficient identification and quantification of outer retinal atrophy and its progression over time. It facilitates measurements both in natural history studies and in interventional trials to evaluate new pharmacologic agents designed to limit GA enlargement.

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).

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. 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.

Chorioretinal nocardiosis.

PURPOSE: Description of ocular involvement in a case of disseminated nocardiosis. METHODS: Case report of an immunosuppressed patient displaying a unilateral extramacular choroidal lesion presumed to be due to nocardia species. The patient received sulfonamide treatment for a culture-proven generalized nocardia infection. RESULTS: During follow-up, demarcation, resolution, and secondary development of macular pucker with vitreoretinal traction and macular edema was observed. Visual acuity of the affected eye recovered from initially 20/100 to 20/32 at the end of follow-up. CONCLUSION: Early and appropriate treatment of ocular endogenous nocardiosis can result in a favorable outcome.