Clinical Manifestations and Genetic Analysis of 5 Korean Choroideremia Patients Initially Diagnosed With Retinitis Pigmentosa.

BACKGROUND: To investigate the clinical findings of choroideremia patients and perform genetic analysis by whole-exome sequencing (WES). METHODS: A total of 94 patients initially diagnosed with retinitis pigmentosa (RP) at another hospital, and who visited our hospital for genetic analysis by WES, were included in the study, along with 64 family members. All subjects underwent comprehensive ophthalmic evaluation, including best-corrected visual acuity, slit lamp examination, fundus photography, fundus autofluorescence (FAF), fluorescein angiography (FAG), visual field (VF), electroretinogram (ERG), and optical coherence tomography (OCT). RESULTS: In six male patients with suspected choroideremia, extensive retinal pigment epithelium (RPE) and severe loss of choroid were observed in the fundus, but not in the macula. CHM gene mutation was confirmed in five patients. A novel single nucleotide variant at a splice site was observed in one patient. OCT showed marked thinning of the outernuclear layer and choroid, except in the macula. FAF showed a small area of hyperfluorescence in the posterior pole. In addition, characteristic interlaminar bridges were observed in four patients. On FAG, hypofluorescence was seen up to the far-peripheral retina in five patients. CONCLUSION: Of the 94 patients initially diagnosed with RP, CHM mutation was identified in five (5.3%) by WES. Choroideremia should be considered as a differential diagnosis of RP. WES would be useful for identifying the causes of hereditary retinal disease.

The Use of Fundus Autofluorescence in Dry Age-Related Macular Degeneration

Fundus autofluorescence (FAF) has been a well-known imaging method for quite some time. However, with developing technologies and novel imaging devices, FAF is being used more often to diagnose and monitor retinal diseases. The density of lipofuscin (LF) and other fluorophores in the retina have a determining role in FAF images. In dry age-related macular degeneration (AMD), hyperautofluorescence is seen in cases of increasing LF in the retina pigment epithelium, whereas hypoautofluorescence is detected in decreasing LF resulting from geographic atrophy. In recent years, studies have shown that FAF images provide prognostic information in patients with AMD. This review aims to highlight the importance of FAF imaging in dry AMD.

Fluorescein angiography versus optical coherence tomography angiography: FA vs OCTA Italian Study.

PURPOSE: To assess the current role of fluorescein angiography after the introduction of optical coherence tomography angiography in real-life clinical practice. METHODS: This was a multicentric retrospective observational study to evaluate the number of fluorescein angiography and optical coherence tomography angiography procedures performed by different devices from January 2013 to December 2018. The centers involved were Centro Italiano Macula (Rome), and ophthalmology departments of University "G. D'Annunzio" Chieti-Pescara (Chieti) and "Azienda Ospedaliero Universitaria Careggi" (Florence). RESULTS: Out of 19,898 total fluorescein angiography procedures performed in the observation period, 3444 (17.3%) were in 2013, 3972 (19.9%) were in 2014, 3601 (18.1%) were in 2015, 3407 (17.2%) were in 2016, 3285 (16.5%) were in 2017, and 2189 (11%) were in 2018. Out of 7949 optical coherence tomography angiography procedures performed in the observation period, none were performed in 2013, 550 (6.9%) were in 2014, 908 (11.5%) were in 2015, 2098 (26.4%) were in 2016, 2090 (26.3%) were in 2017, and 2303 (28.9%) were in 2018. CONCLUSION: Fluorescein angiography procedures were performed less often after the introduction of optical coherence tomography angiography technology. The ease, speed, and safety of the optical coherence tomography angiography procedure in everyday clinical practice have facilitated more optical coherence tomography angiography application compared to fluorescein angiography in recent years. In the future, we will probably evaluate the different pathologies that still need an evaluation by fluorescein angiography.

UTILITY OF ORAL FLUORESCEIN ANGIOGRAPHY WITH ULTRA-WIDEFIELD IMAGING SYSTEM FOR EVALUATION OF VARIOUS RETINAL DISORDERS.

PURPOSE: To evaluate the utility of oral fluorescein angiography with ultra-widefield imaging system (oral UWF-FA) predominantly in children. METHODS: We recruited 17 patients aged 2 years to 22 years with retinal disorders. Each patient ingested a dose of fluorescein sodium set by body weight mixed with 100 mL of juice. Images were scored using four parameters as follows: branch retinal vessel identification, retinal vessels visualization, foveal avascular zone visualization, and clinically important findings such as leakage, microaneurysms, neovascularization, or significant nonperfusion area visualization. Based on the aggregate score, we classified the image quality into three grades. RESULTS: Sixteen of 17 patients completely ingested the fluorescein sodium, and ultra-widefield fluorescein angiography was performed. Images were classified as high quality in nine cases, moderate quality in four, and poor quality in three. In 13 cases (81.3%), images had adequate quality to evaluate retinal conditions. Of three patients with poor-quality images, 2 took 10 minutes to ingest fluorescein sodium and the other ingested only half the dose. The adverse event of a mild skin rash was noted in one patient. CONCLUSION: Oral ultra-widefield fluorescein angiography is effective in evaluating retinal pathology and is a useful alternative especially for pediatric patients who cannot tolerate intravenous line placement.

Automated vessel density detection in fluorescein angiography images correlates with vision in proliferative diabetic retinopathy.

PURPOSE: To investigate the correlation between quantifiable vessel density, computed in an automated fashion, from ultra-widefield fluorescein angiography (UWFFA) images from patients with proliferative diabetic retinopathy (PDR) with visual acuity and macular thickness. METHODS: We performed a secondary analysis of a prospective randomized controlled trial. We designed and trained an algorithm to automate retinal vessel detection from input UWFFA images. We then used our algorithm to study the correlation between baseline vessel density and best corrected visual acuity (BCVA) and CRT for patients in the RECOVERY study. Reliability of the algorithm was tested using the intraclass correlation (ICC). 42 patients from the Intravitreal Aflibercept for Retinal Non-Perfusion in Proliferative Diabetic Retinopathy (RECOVERY) trial who had both baseline UWFFA images and optical coherence tomography (OCT) data were included in our study. These patients had PDR without significant center-involving diabetic macular edema (central retinal thickness [CRT] ≤320µm). RESULTS: Our algorithm analyzed UWFFA images with a reliability measure (ICC) of 0.98. A positive correlation (r = 0.4071, p = 0.0075) was found between vessel density and BCVA. No correlation was found between vessel density and CRT. CONCLUSIONS: Our algorithm is capable of reliably quantifying vessel density in an automated fashion from baseline UWFFA images. We found a positive correlation between computed vessel density and BCVA in PDR patients without center-involving macular edema, but not CRT. TRANSLATIONAL RELEVANCE: Our work is the first to offer an algorithm capable of quantifying vessel density in an automated fashion from UWFFA images, allowing us to work toward studying the relationship between retinal vascular changes and important clinical endpoints, including visual acuity, in ischemic eye diseases.

Agreement in Measures of Macular Perfusion between Optical Coherence Tomography Angiography Machines.

We evaluated the agreements in foveal avascular zone (FAZ) area and vessel density (VD) parameters (within the superficial capillary plexus region), between two widely used optical coherence tomography angiography machines. Participants who attended the Singapore Malay Eye Study III between 29th March and 6th August 2018, were enrolled in this study. Participants underwent fovea-centered 6×6-mm macular cube scan, using both AngioVue and Cirrus HDOCT machines. Scans were analyzed automatically using built-in review software of each machine. 177 eyes (95 participants) without retinal diseases were included for final analysis. Mean FAZ area was 0.38 ± 0.11 mm2 and 0.30 ± 0.10 mm2, based on AngioVue and Cirrus HDOCT, respectively. Mean parafoveal VD was 0.50 ± 0.04 in Angiovue, and 0.43 ± 0.04 in Cirrus HDOCT. Cirrus HDOCT measurements were consistently lower than those by AngioVue, with a mean difference of -0.08 (95% limits of agreement [LOA], -0.30-0.13) mm2 for FAZ area, and -0.07 (95% LOA, -0.17-0.03) for parafoveal VD. Intraclass correlation coefficients for FAZ area and parafoveal VD were 0.33 and 0.07, respectively. Our data suggest that agreements between AngioVue and Cirrus HDOCT machines were poor to fair, thus alternating use between these two machines may not be recommended especially for follow up evaluations.

[Indications for fluorescein angiography and optical coherence tomography angiography (OCTA) in medical retina: Changes from 2015 and 2018]. / Indications d'angiographie à la fluorescéine et d'OCT-angiographie en consultation de rétine médicale : comparaison entre 2015 et 2018.

INTRODUCTION: Non-invasive multimodal imaging, including optical coherence tomography angiography (OCTA), has demonstrated high sensitivity and specificity for the management of retinal diseases. Since the availability of OCTA in 2015, we have developed a policy of "as little fluorescein angiography as possible". In this study, we describe the rate of OCTA and fluorescein angiography (FA) performed and their indications. METHODS: Retrospective descriptive single-centre study. Chart review of patients examined for retinal disorders by one medical retina specialist between January 2015 and June 2018. RESULTS: 3487 patients were examined for a retinal disease. The charts of 651 of these patients (1170 eyes) were randomly selected for analysis (study group). The mean age in the study group was 72 years (60% female). Overall, OCTA and FA were performed in 49.4% and 6.5% of the studied eyes respectively. After the first year, the rate of FA decreased to 2%. The main indications for OCTA were age-related macular degeneration (AMD): 50%, central serous chorioretinopathy (CSC): 12% and retinal vascular occlusion: 10%. The most frequent indications for FA were AMD: 49%, diabetic retinopathy (DR): 18% and CSC: 14%. FA was performed in 16%, 11% and 10% of eyes diagnosed with DR, CSC and AMD respectively (P<0.05). CONCLUSION: In routine practice, OCTA was performed in half of the eyes examined for a retinal disorder. The overall rate of FA was 6.5% and dropped to 2% after the first year of OCTA use. DR was the main disorder still requiring FA.

Screening and Follow-Up of Acute ROP: Reproducibility of Fluorescein Angiography.

INTRODUCTION: Binocular indirect ophthalmoscopy (BIO) is fundamental for screening of retinopathy of prematurity (ROP). Digital retinal imaging devices with fluorescein angiography (FA) proved to be useful in screening and management of ROP. FA provides valuable additional information that is not detectable through ophthalmoscopy. FA images are relatively easy to interpret even by personnel without specific experience in ROP. The aim of this study is to evaluate reproducibility of FA for the screening and follow-up of ROP. METHODS: A total of 106 pairs of FA images of 30 eyes of 15 premature infants with stage II ROP were evaluated by 5 ophthalmologists: 2 experts, 2 non-experts, and 1 expert in reading FA in adult patients. Each operator gave a score to each of following parameters: leakage, ischemic areas, peripheral plus disease and vascular anomalies. The images were reviewed twice. Intra- and inter-concordance between the readers of the FA findings was evaluated by the means of Cohen's kappa coefficient (κ). RESULTS: The intra-operator concordance was very good (κ > 0.81) for all FA findings. Inter-operator concordance was good (κ > 0.41) for all operators and all FA findings. Global concordance was: substantial (intra-inter readers: κ > 0.61) for leakage, ischemic areas, and plus disease; almost perfect (κ > 0.81) for vascular anomalies; and moderate (κ = 0.41-0.60) for continuity/discontinuity of the ischemic areas. Total FA score was directly correlated to the percentage of treatment: a score ≥ 7 was correlated with 100% treatment and a score ≤ 3 with no treatment. Treatment timing was inversely correlated to FA score: a score ≥ 8 was correlated with a timely treatment (≤ 6 days), and a score ≤ 7 was correlated with a delayed treatment (< 10 days). CONCLUSION: This study showed that FA represents a reproducible imaging technique. It is useful for detecting ROP progression, and to define the treatment timing and type.

Topological data analysis of high resolution diabetic retinopathy images.

Diabetic retinopathy is a complication of diabetes that produces changes in the blood vessel structure in the retina, which can cause severe vision problems and even blindness. In this paper, we demonstrate that by identifying topological features in very high resolution retinal images, we can construct a classifier that discriminates between healthy patients and those with diabetic retinopathy using summary statistics of these features. Topological data analysis identifies the features as connected components and holes in the images and describes the extent to which they persist across the image. These features are encoded in persistence diagrams, summaries of which can be used to discrimate between diabetic and healthy patients. The method has the potential to be an effective automated screening tool, with high sensitivity and specificity.

UTILITY OF ULTRA-WIDEFIELD RETINAL IMAGING FOR THE STAGING AND MANAGEMENT OF SICKLE CELL RETINOPATHY.

PURPOSE: To determine whether ultra-widefield (UWF) retinal imaging changes the staging or management of sickle cell retinopathy compared with clinical examination. METHODS: Prospective, observational study including patients with sickle cell disease. All patients underwent dilated fundus examination by a fellowship-trained retina specialist, as well as UWF fundus photography (FF) and fluorescein angiography (FA). Sickle retinopathy stage and treatment recommendation per eye were determined after clinical examination, UWF-FF, and UWF-FA, respectively, and differences in retinopathy stage and treatment recommendation were compared. RESULTS: A total of 70 eyes from 35 patients (17 women, 48.6%), mean age 30.4 years, were included. Sickle genotypes included 26 patients with sickle SS (74.3%), 7 SC (20.0%), and 2 ß(+)thalassemia (5.7%). Based on examination, most eyes (42/70; 60.0%) had no visible retinopathy. Based on UWF-FF, about half of the eyes were found to be Goldberg Stage 2 or above (36/70; 51.4%). Based on UWF-FA, nearly all eyes were Goldberg Stage 2 or above (63/70; 90%). However, clinical examination reliably detected neovascularization, and in no case did the addition of UWF imaging change management relative to examination alone. CONCLUSION: Ultra-widefield imaging detects a higher stage of sickle cell retinopathy compared with clinical examination alone, but these differences may not be clinically significant.

Fluorescein Angiography Indications: Changes after Optical Coherence Tomography and Antiangiogenics.

SIGNIFICANCE: The present study provides quantitative data regarding the change of indications of fluorescein angiography in a tertiary hospital. Exhaustively compiled data over more than 10 years concerning all the angiographic studies including diagnosis, first-visit/follow-up, possible relation with antiangiogenics approval, and optic coherence tomography (OCT) are presented. PURPOSE: The aim of this study was to determine the frequency and indications of fluorescein angiography before and after OCT and anti-vascular endothelial growth factor (anti-VEGF) treatment implantation. METHODS: This was a retrospective and descriptive study of all fluorescein angiographies performed in a tertiary hospital between 2005 and 2016. Demographic data, diagnosis, follow-up, and type of angiograms were analyzed in relation with the implantation of time domain OCT (2006), spectral domain OCT (SD-OCT) (2013), and anti-VEGF (2007). RESULTS: Of 3263 angiograms (2342 patients) analyzed, 72% were baseline angiograms, and 28% were follow-up angiograms. After anti-VEGF initiation, the number of angiograms per year increased progressively with peaks that matched with the approval of anti-VEGF for wet age-related macular degeneration (2007) (164.2%), macular edema secondary to retinal vein occlusions (2010) (102.2%), and diabetic macular edema (2011) (123.8%). After using SD-OCT, fluorescein angiographies decreased up to 57%. CONCLUSIONS: Anti-VEGF introduction led to an increase in the indication of angiograms, which did not vary significantly after time domain OCT. Nevertheless, since SD-OCT became available, the indication of fluorescein angiography has halved in the hospital of reference.

Inter-Rater Reliability of Cyclotorsion Measurements Using Fundus Photography.

BACKGROUND: The foveo-papillary angle (FPA) on fundus photographs is the accepted standard for the measurement of ocular cyclotorsion. We assessed the inter-rater reliability of this method in healthy subjects and in patients with trochlear nerve palsies. PATIENTS AND METHODS: In this methodological study, fundus photographs of healthy subjects and of patients with trochlear nerve palsies were made with a fundus camera (Zeiss Fundus Camera FF 450 plus, Jena, Germany). Three independent observers measured the FPA on the fundus photographs of all subjects in synedra View (synedra View 16, Version 16.0.0.11, Innsbruck, Austria). RESULTS: One hundred and four eyes of 52 subjects (26 healthy controls and 26 patients) were assessed. The mean FPA of the healthy controls was 5.80 degrees (°) [± 0.44 standard error of the mean (SEM)] compared to 11.55° (± 0.80 SEM) for patients with trochlear nerve palsies. The inter-rater reliability of all measured FPAs showed an intraclass correlation coefficient (ICC) of 0.98 (95% CI 0.97 - 0.98). CONCLUSIONS: The inter-rater reliability of objective cyclotorsion measurements using fundus photographs was very high.

Optical techniques for perfusion monitoring of the gastric tube after esophagectomy: a review of technologies and thresholds.

Anastomotic leakage is one of the most severe complications after esophageal resection with gastric tube reconstruction. Impaired perfusion of the gastric fundus is seen as the main contributing factor for this complication. Optical modalities show potential in recognizing compromised perfusion in real time, when ischemia is still reversible. This review provides an overview of optical techniques with the aim to evaluate the (1) quantitative measurement of change in perfusion in gastric tube reconstruction and (2) to test which parameters are the most predictive for anastomotic leakage.A Pubmed, MEDLINE, and Embase search was performed and articles on laser Doppler flowmetry (LDF), near-infrared spectroscopy (NIRS), laser speckle contrast imaging (LSCI), fluorescence imaging (FI), sidestream darkfield microscopy (SDF), and optical coherence tomography (OCT) regarding blood flow in gastric tube surgery were reviewed. Two independent reviewers critically appraised articles and extracted the data: Primary outcome was quantitative measure of perfusion change; secondary outcome was successful prediction of necrosis or anastomotic leakage by measured perfusion parameters.Thirty-three articles (including 973 patients and 73 animals) were selected for data extraction, quality assessment, and risk of bias (QUADAS-2). LDF, NIRS, LSCI, and FI were investigated in gastric tube surgery; all had a medium level of evidence. IDEAL stage ranges from 1 to 3. Most articles were found on LDF (n = 12), which is able to measure perfusion in arbitrary perfusion units with a significant lower amount in tissue with necrosis development and on FI (n = 12). With FI blood flow routes could be observed and flow was qualitative evaluated in rapid, slow, or low flow. NIRS uses mucosal oxygen saturation and hemoglobin concentration as perfusion parameters. With LSCI, a decrease of perfusion units is observed toward the gastric fundus intraoperatively. The perfusion units (LDF, LSCI), although arbitrary and not absolute values, and low flow or length of demarcation to the anastomosis (FI) both seem predictive values for necrosis intraoperatively. SDF and OCT are able to measure microvascular flow, intraoperative prediction of necrosis is not yet described.Optical techniques aim to improve perfusion monitoring by real-time, high-resolution, and high-contrast measurements and could therefore be valuable in intraoperative perfusion mapping. LDF and LSCI use perfusion units, and are therefore subjective in interpretation. FI visualizes influx directly, but needs a quantitative parameter for interpretation during surgery.

The use of optical coherence tomography angiography in pachychoroid spectrum diseases: a concurrent comparison with dye angiography.

PURPOSE: The study objective was to compare dye angiography and optical coherence tomography angiography (OCTA) in detecting choroidal neovascuarization (CNV) in patients presenting with pachychoroid features and flat irregular pigment epithelial detachment (PED). METHODS: Nineteen eyes of 17 patients, presenting with flat PED and pachychoroid features, and without age-related macular degeneration or any other degenerative change, were analyzed. Fuorescein angiography (FA)/Indocyanine green angiography (ICGA) and OCTA were performed during the same visit. Subfoveal choroidal thickness was measured by enhanced depth imaging using spectral domain optical coherence tomography. RESULTS: The mean age of the patients was 59.1 years. Mean subfoveal choroidal thickness was 388 µm. FA revealed non-patognomic features including RPE alterations, window defects, leaking points and leakage from an undetermined source. ICGA revealed choroidal vascular plaque in eight eyes (42%) and suspicious plaque in five eyes (26%). Nonneovascular features, such as hyperpermeability or dilated choroidal vessels, were observed in six eyes (32%). OCTA showed choroidal neovascularization in 14 (74%). For all of the eyes, which ICGA was positive for presence of CNV, OCTA also showed CNV, and in one case it also revealed polypoidal characteristics of the neovascular network. OCTA was also able to detect CNV in all of the eyes with suspicious plaque, and in one eye without CNV appearance using ICGA. CONCLUSIONS: OCTA demonstrated greater sensitivity in detecting type 1 CNV than conventional dye angiography in cases with pachychoroid spectrum disease.

Are we making good use of our public resources? The false-positive rate of screening by fundus photography for diabetic macular oedema.

INTRODUCTION: A large proportion of patients diagnosed with diabetic maculopathy using fundus photography and hence referred to specialist clinics following the current screening guidelines adopted in Hong Kong and United Kingdom are found to be false-positive, implying that they did not have macular oedema. This study aimed to evaluate the false-positive rate of diabetic maculopathy screening using the objective optical coherence tomography scan. METHODS: This was a cross-sectional observational study. Consecutive diabetic patients from the Hong Kong West Cluster Diabetic Retinopathy Screening Programme with fundus photographs graded R1M1 were recruited between October 2011 and June 2013. Spectral-domain optical coherence tomography imaging was performed. Central macular thickness of ≥300 µm and/or the presence of optical coherence tomography signs of diabetic macular oedema were used to define the presence of diabetic macular oedema. Patients with conditions other than diabetes that might affect macular thickness were excluded. The mean central macular thickness in various subgroups of R1M1 patients was calculated and the proportion of subjects with central macular thickness of ≥300 µm was used to assess the false-positive rate of this screening strategy. RESULTS: A total of 491 patients were recruited during the study period. Of the 352 who were eligible for analysis, 44.0%, 17.0%, and 38.9% were graded as M1 due to the presence of foveal 'haemorrhages', 'exudates', or 'haemorrhages and exudates', respectively. The mean (±standard deviation) central macular thickness was 265.1±55.4 µm. Only 13.4% (95% confidence interval, 9.8%-17.0%) of eyes had a central macular thickness of ≥300 µm, and 42.9% (95% confidence interval, 37.7%-48.1%) of eyes had at least one optical coherence tomography sign of diabetic macular oedema. For patients with retinal haemorrhages only, 9.0% (95% confidence interval, 4.5%-13.5%) had a central macular thickness of ≥300 µm; 23.2% (95% confidence interval, 16.6%-29.9%) had at least one optical coherence tomography sign of diabetic macular oedema. The false-positive rate of the current screening strategy for diabetic macular oedema was 86.6%. CONCLUSION: The high false-positive rate of the current diabetic macular oedema screening adopted by the United Kingdom and Hong Kong may lead to unnecessary psychological stress for patients and place a financial burden on the health care system. A better way of screening is urgently needed. Performing additional spectral-domain optical coherence tomography scans on selected patients fulfils this need.

Discrepancies between Spectral Domain Optical Coherence Tomography and Fluorescein Angiography in Detecting Uveitic Macular Edema.

AIM: To compare spectral-domain optical coherence tomography (SD-OCT) with fluorescein angiography (FA) in detecting macular edema in patients with uveitis and analyse discrepancies in the findings obtained by the two methods. METHODS: The study included 133 eyes from 117 patients with uveitis that had SD-OCT (RTVue-100/ Optovue) and FA (Topcon TRC 50DX) scans performed to detect or rule out macular edema. RESULTS: Macular edema was found in 57 (42.9%) of the 133 surveyed eyes. In 37 eyes (27.8%) macular edema was confirmed by both imaging methods. In 17 eyes (12.8%) macular edema was detected on SD-OCT but not on FA;in 15 eyes of these the edema was diffuse, and in 2 eyes - serous retinal detachment was verified in the macular area. Focal macular edema was detected on FA in three eyes (2.3%) in which SD-OCT showed normal finding. In 76 eyes (57.1%) no pathological changes in the macula were observed on both SD-OCT and FA. Kappa coefficient was 0.675 at p < 0.001. The agreement rate between the two methods calculated using Kendall's tau-b was 0.693 at p < 0.001. CONCLUSION: Fluorescein angiography and spectral domain optical coherence tomography are highly sensitive methods used in detecting macular edema in patients with uveitis, but they might fail to be efficient in this if used independently. Optical coherence tomography is a more informative method, especially in diagnosing diffuse macular edema.

Fluorescence microangiography for quantitative assessment of peritubular capillary changes after AKI in mice.

AKI predicts the future development of CKD, and one proposed mechanism for this epidemiologic link is loss of peritubular capillaries triggering chronic hypoxia. A precise definition of changes in peritubular perfusion would help test this hypothesis by more accurately correlating these changes with future loss of kidney function. Here, we have adapted and validated a fluorescence microangiography approach for use with mice to visualize, analyze, and quantitate peritubular capillary dynamics after AKI. A novel software-based approach enabled rapid and automated quantitation of capillary number, individual area, and perimeter. After validating perfusion in mice with genetically labeled endothelia, we compared peritubular capillary number and size after moderate AKI, characterized by complete renal recovery, and after severe AKI, characterized by development of interstitial fibrosis and CKD. Eight weeks after severe AKI, we measured a 40%±7.4% reduction in peritubular capillary number (P<0.05) and a 36%±4% decrease in individual capillary cross-sectional area (P<0.001) for a 62%±2.2% reduction in total peritubular perfusion (P<0.01). Whereas total peritubular perfusion and number of capillaries did not change, we detected a significant change of single capillary size following moderate AKI. The loss of peritubular capillary density and caliber at week 8 closely correlated with severity of kidney injury at day 1, suggesting irreparable microvascular damage. These findings emphasize a direct link between severity of acute injury and future loss of peritubular perfusion, demonstrate that reduced capillary caliber is an unappreciated long-term consequence of AKI, and offer a new quantitative imaging tool for understanding how AKI leads to future CKD in mouse models.

Reduced fluorescein angiography and fundus photography use in the management of neovascular macular degeneration and macular edema during the past decade.

PURPOSE: We assessed recent trends in the use of diagnostic testing for neovascular age-related macular degeneration (NVAMD) and macular edema (ME). METHODS: Claims data from a managed-care network were analyzed on patients with NVAMD (n = 22,954) or ME (n = 31,810) to assess the use of fluorescein angiography (FA), fundus photography (FP), and optical coherence tomography (OCT) from 2001 to 2009. Repeated-measures logistic regression was performed to compare patients' odds of undergoing these procedures in 2001, 2005, and 2009. In addition, the proportions of patients with an incident NVAMD or ME diagnosis in 2003 or 2008 who underwent FA, FP, and OCT were compared. RESULTS: From 2001 to 2009, among patients with NVAMD, the odds of undergoing OCT increased 23-fold, whereas the odds of receiving FA and FP decreased by 68% and 79%, respectively. Similar trends were observed for ME. From 2003 to 2008, the proportion of patients undergoing OCT within 1 year of initial diagnosis increased by 315% for NVAMD and by 143% for ME; the proportion undergoing OCT without FA within 1 year increased by 463% for NVAMD and by 216% for ME. CONCLUSIONS: Use of OCT increased dramatically during the past decade, whereas use of FA and FP declined considerably, suggesting that OCT may be replacing more traditional diagnostic testing in patients with NVAMD or ME. Future studies should evaluate whether this increased reliance on OCT instead of FA and FP affects patient outcomes.

[Fundus screening by medical technicians]. / Fundusscreening durch Assistenzpersonal.

Ocular fundus photography allows detection of both ocular and systemic diseases. This study investigated the efficacy of a broad screening in a department of internal medicine using nonmydriatic digital fundus photography. For 8 weeks a medical technician was trained in using the camera as well as interpreting the photographs. The medical technician and an ophthalmologist evaluated the fundus photographs separately by using a self-developed questionnaire. The fundus camera was user-friendly and after several weeks of adjustment and practical application the medical technician was able to detect the majority of pathological fundus photographs. Out of 218 patients examined 148 (68%) were identified as pathological by the medical technician and 163 (75%) by the ophthalmologist (p = 0.0003). The medical technician missed 15 (7%) patients. Furthermore the diagnoses made by the medical technician were faulty. In summary an ophthalmological screening by a medical technician is feasible but the diagnosis still remains the responsibility of ophthalmologists. Such a compromise could facilitate the examination of a large number of patients and disclose previously unrecognized diseases.

Dynamic indocyanine green angiography measurements.

Dynamic indocyanine green imaging uses a scanning laser ophthalmoscope and a fluorescent dye to produce movies of the dye-filling pattern in the retina and choroid of the eye. It is used for evaluating choroidal neovascularization. Movies are examined to identify the anatomy of the pathology for planning treatment and to evaluate progression or response to treatment. The popularity of this approach is affected by the complexity and difficulty in interpreting the movies. Software algorithms were developed to produce images from the movies that are easy to interpret. A mathematical model is formulated of the flow dynamics, and a fitting algorithm is designed that solves for the flow parameters. The images provide information about flow and perfusion, including regions of change between examinations. Imaged measures include the dye fill-time, temporal dispersion, and magnitude of the dye dilution temporal curves associated with image pixels. Cases show how the software can help to identify clinically relevant anatomy such as feeder vessels, drain vessels, capillary networks, and normal choroidal draining vessels. As a potential tool for research into the character of neovascular conditions and treatments, it reveals the flow dynamics and character of the lesion. Future varieties of this methodology may be used for evaluating the success of engineered tissue transplants, surgical flaps, reconstructive surgery, breast surgery, and many other surgical applications where flow, perfusion, and vascularity of tissue are important.