Optical coherence tomography angiography for the detection of macular neovascularization-comparison of en face versus cross-sectional view.

PURPOSE: To evaluate sensitivity and specificity of swept source-optical coherence tomography angiography (SS-OCTA) en face images versus cross-sectional OCTA versus a combination of both for the detection of macular neovascularization (MNV). DESIGN: Prospective cohort study. PARTICIPANTS: Consecutive patients with various chorioretinal diseases and subretinal hyperreflective material (SHRM) and/or pigment epithelial detachment (PED) on OCT possibly corresponding to MNV in at least one eye. METHODS: 102 eyes of 63 patients with fluorescein angiography (FA), OCT and SS-OCTA performed on the same day were included. FA images, the outer retina to choriocapillaris (ORCC) OCTA en face slab, a manually modified en face slab ('custom slab'), cross-sectional OCTA and a combination of OCTA en face and cross-section were evaluated for presence of MNV. MAIN OUTCOME MEASURES: Sensitivity and specificity for MNV detection, as well as the concordance was calculated using FA as the reference. RESULTS: OCTA en face imaging alone yielded a sensitivity of 46.3% (automated)/78.1% (custom) and specificity of 93.4% (automated)/88.5% (custom) for MNV detection. Cross-sectional OCTA (combination with en face) resulted in a sensitivity of 85.4% (82.9%) and specificity of 82.0% (85.3%). Concordance to FA was moderate for automated en face OCTA (κ = 0.43), and substantial for custom en face OCTA (κ = 0.67), cross-sectional OCTA (κ = 0.66) and the combination (κ = 0.68). CONCLUSION: Segmentation errors result in decreased sensitivity for MNV detection on automatically generated OCTA en face images. Cross-sectional OCTA allows detection of MNV without manual modification of segmentation lines and should be used for evaluation of MNV on OCTA.

LONG-TERM FOLLOW-UP OF ASYMMETRIC BILATERAL DIFFUSE UVEAL MELANOCYTIC PROLIFERATION IN A PATIENT WITH METASTASIZED UROTHELIAL CARCINOMA.

PURPOSE: To report a case of bilateral diffuse uveal melanocytic proliferation over 30 months follow-up. METHODS: Multimodal imaging including ultra-wide-field color fundus photography, blue light fundus autofluorescence, swept-source optical coherence tomography, fluorescein angiography, and indocyanine green angiography. RESULTS: A 49-year-old woman presented with decreased vision 2 months after bladder cancer surgery. Exudative retinal detachment and leopard spot pattern chorioretinopathy were observed in the right eye. Chemotherapy and cystectomy were initiated. Progressive bilateral vision loss occurred with melanocytic proliferation, choroidal thickening, subretinal fibrosis, fluid extravasation, rapid development of mature cataract, multiple iris cysts, and rubeosis, despite plasmapheresis and IV immunoglobulins. After cataract surgery, massive fibrin reaction resulted in a ciliolenticular block. One year later, positron emission tomography-computed tomography revealed absence of metastases. At Month 23, choroidal thickness increased in line with tumor progression. Palliative systemic therapy was initiated. Secondary macular neovascularization was treated with intravitreal antivascular endothelial growth factor injections. Visual acuity was light perception in the right eye and 20/200 in the left eye at last follow-up. CONCLUSION: Bilateral diffuse uveal melanocytic proliferation results in progressive melanocyte proliferation and exudation, leading to severe visual loss. In our case, visual acuity was preserved at a low level in one eye under continuous systemic treatment. Systemic corticosteroids are recommended for cataract surgery in the setting of bilateral diffuse uveal melanocytic proliferation to prevent massive fibrin reaction. Intravitreal antivascular endothelial growth factor injections may be indicated if secondary macular neovascularization develops.

Transferability of an Artificial Intelligence Algorithm Predicting Rebubblings After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To develop an artificial intelligence (AI) algorithm enabling corneal surgeons to predict the probability of rebubbling after Descemet membrane endothelial keratoplasty (DMEK) from images obtained using optical coherence tomography (OCT). METHODS: Anterior segment OCT data of patients undergoing DMEK by 2 different DMEK surgeons (C.C. and B.B.; University of Cologne, Cologne, Germany) were extracted from the prospective Cologne DMEK database. An AI algorithm was trained by using a data set of C.C. to detect graft detachments and predict the probability of a rebubbling. The architecture of the AI model used in this study was called EfficientNet. This algorithm was applied to OCT scans of patients, which were operated by B.B. The transferability of this algorithm was analyzed to predict a rebubbling after DMEK. RESULTS: The algorithm reached an area under the curve of 0.875 (95% confidence interval: 0.880-0.929). The cutoff value based on the Youden index was 0.214, and the sensitivity and specificity for this value were 78.9% (67.6%-87.7%) and 78.6% (69.5%-86.1%). CONCLUSIONS: The development of AI algorithms allows good transferability to other surgeons reaching a high accuracy in predicting rebubbling after DMEK based on OCT image data.

Comparison of swept-source versus spectral-domain optical coherence tomography angiography for detection of macular neovascularization.

PURPOSE: To compare swept-source (SS) versus spectral-domain (SD) optical coherence tomography angiography (OCTA) for the detection of macular neovascularization (MNV). METHODS: In this prospective cohort study, 72 eyes of 54 patients with subretinal hyperreflective material (SHRM) and/or pigment epithelial detachment (PED) on OCT possibly corresponding to MNV in at least one eye were included. OCTA scans were acquired using two devices, the PLEX Elite 9000 SS-OCTA and the Spectralis SD-OCTA. Fluorescein angiography (FA) was used as reference. Two graders independently evaluated en face OCTA images using a preset slab as well as a manually modified slab, followed by a combination of en face and cross-sectional OCTA. RESULTS: Sensitivity (specificity) for the automated slabs was 51.7% (93.0%) for SS-OCTA versus 58.6% (95.3%) for SD-OCTA. Manual modification of segmentation increased sensitivity to 79.3% for SS-OCTA but not for SD-OCTA (58.6%). The combination of en face OCTA with cross-sectional OCTA reached highest sensitivity values (SS-OCTA: 82.8%, SD-OCTA: 86.2%), and lowest number of cases with discrepancies between SS-OCTA and SD-OCTA (4.2%). Fleiss kappa as measure of concordance between FA, SS-OCTA, and SD-OCTA was 0.56 for the automated slabs, 0.60 for the manual slabs, and 0.73 (good agreement) for the combination of en face OCTA with cross-sectional OCTA. Concordance to FA was moderate for the automated slabs and good for manual slabs and combination with cross-sectional OCTA of both devices. CONCLUSION: Both devices reached comparable results regarding the detection of MNV on OCTA. Sensitivity for MNV detection and agreement between devices was best when evaluating a combination of en face and cross-sectional OCTA.

Corneal densitometry: a potential indicator for early diagnosis of Fabry disease.

PURPOSE: To assess corneal densitometry in patients with Fabry disease (FD) and to compare corneal densitometry differences in FD patients to different corneal manifestations. METHODS: Ten participants (20 eyes) with FD and 10 age-matched healthy volunteers (20 eyes) were recruited. All participants were assessed by standardized ophthalmic examinations and the corneal densitometry analysis by Pentacam HR. Densitometry measurements were analyzed in standardized grayscale units. RESULTS: Seven patients developed conjunctival vessel tortuosity, cornea verticillata appeared in 6 patients, and two patients had Fabry cataract. Retinal vessel tortuosity occurred in 4 patients, and dilation of retinal vessels appeared in 3 patients, all symptoms occurred in both eyes. The first diagnosis of FD up to examination was 4.7 ± 3.23 years, and first ERT up to examination was 2.6 ± 2.27 years. The initial time to diagnosis was negatively related to the corneal densitometry value of the 0-2-mm (r = - 0.556, p = 0.011) and 2-6-mm (r = - 0.482, p = 0.032) zones in the posterior layer. FD group have significantly higher corneal densitometry in anterior 0-2-mm zone and 2-10-mm zone anterior and posterior layer than the control group (p ≤ 0.035, respectively). When divided into two groups by the existence of cornea verticillata, there was a statistically significant difference in the anterior layer, 6-10-mm zone (p = 0.031); in the central layer, 0-2 mm (p = 0.012), 2-6 mm (p = 0.001), 6-10 mm (p = 0.002), and total (p = 0.002); and in the posterior layer, 6-10 mm (p = 0.004) and total (p = 0.002). CONCLUSIONS: FD patients show higher corneal densitometry, and corneal densitometry may have potential for early diagnosis and reminding progress of FD.

Absence of lymphatic vessels in non-functioning bleb capsules of glaucoma drainage devices.

PURPOSE: To evaluate the presence and appearance of blood and lymphatic vessels in non-functioning bleb capsules of glaucoma drainage devices (GDD). MATERIALS AND METHODS: Non-functioning (n=14) GDD-bleb capsules of 12 patients were analyzed by immunohistochemistry for blood vessels (CD31, vascular endothelium), lymphatic vessels (lymphatic vessel endothelial hyaluronan receptor-1 [LYVE-1] and podoplanin) and macrophages (CD68). RESULTS: CD31+++ blood vessels and CD68+ macrophages were detected in the outer layer of all specimens. LYVE-1 immunoreactivity was registered in single non-endothelial cells in 8 out of 14 (57%) bleb capsule specimens. Podoplanin-immunoreactivity was detected in all cases, located in cells and profiles of the collagen tissue network of the outer and/or the inner capsule layer. However, a colocalization of LYVE-1 and podoplanin as evidence for lymphatic vessels was not detected. CONCLUSIONS: We demonstrate the presence of blood-vessels but absence of lymphatic vessels in non-functioning bleb capsules after GDD-implantation. While the absence of lymphatic vessels might indicate a possible reason for drainage device failure, this needs to be confirmed in upcoming studies, including animal experiments.

Comparison of Automated versus Manually Modified OCT Angiography En Face Slabs for Detection of Choroidal Neovascularization.

PURPOSE: To evaluate the sensitivity and specificity for the detection of choroidal neovascularization (CNV) using automatically generated versus manually modified swept-source OCT angiography (SS-OCTA) en face images. DESIGN: Prospective cohort study. PARTICIPANTS: Consecutive patients with various chorioretinal diseases and subretinal hyperreflective material (SHRM) or pigment epithelial detachments (PEDs) on OCT possibly corresponding to CNV in at least 1 eye. METHODS: A total of 102 eyes of 63 patients were included in this study. Fluorescein angiography (FA) and SS-OCTA imaging (PLEX Elite 9000, Carl Zeiss Meditec, Dublin, CA) were performed at the same day. OCTA en face images were generated using the "retina," "avascular," "choriocapillaris," and "outer retina to choriocapillaris (ORCC)" slabs automatically provided by the software. In addition, a custom slab was created by manual modification of the automatically provided boundary "retinal pigment epithelium fit" positioned at the level of Bruch's membrane and anterior to any SHRM or PED to ensure that a possible CNV was captured in its entirety. Two graders independently evaluated OCTA en face images for the presence of CNV masked to all other images of the patient. MAIN OUTCOME MEASURES: Sensitivity and specificity for detection of CNV using FA as the reference. RESULTS: In 40% of cases (41/102), a CNV was detected on FA. Automatically provided OCTA en face slabs revealed the highest sensitivity for the "ORCC" slab (46.3%), followed by the "retina" slab (22.0%), "avascular" slab (17.1%), and "choriocapillaris" slab (14.6%). Specificity ranged between 93.4% for "ORCC" and 100% for the "retina" and "avascular" slabs. Sensitivity could be increased to 78.1% using the custom slab with a specificity of 88.5%. Concordance between FA and OCTA en face slabs was moderate for the "ORCC" slab (κ = 0.43; range, 0.41-0.60) and substantial for the custom slab (κ = 0.67; range, 0.61-0.80). CONCLUSIONS: Segmentation artifacts and incomplete coverage of CNV on SS-OCTA en face images may impede identification of CNV. Manual modification of the position of automatically generated segmentation lines anterior and posterior to any suspected CNV (SHRM or PED) increases the sensitivity of CNV detection compared with automatically generated slabs.

Changes in Corneal Biomechanical Properties After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To evaluate the course of corneal biomechanical properties (corneal hysteresis and corneal resistance factor) after Descemet membrane endothelial keratoplasty (DMEK) in patients with Fuchs endothelial dystrophy (FECD). METHODS: In this prospective study, we consecutively included 49 patients with FECD with an indication for DMEK. Central corneal thickness, measured using the Oculus Pentacam, and corneal hysteresis (CH) and corneal resistance factor (CRF), both measured using the Reichert Ocular Response Analyzer, were examined preoperatively, 3 months, and 6 months after DMEK. RESULTS: CH was significantly increased 6 months postoperatively (8.66 ± 2.50 mm Hg) compared with preoperative baseline (7.43 ± 1.56 mm Hg). Preoperative CRF (7.89 ± 1.68 mm Hg) increased significantly 6 months after DMEK (8.49 ± 1.71 mm Hg). Preoperative central corneal thickness showed a significant decrease from 629 ± 58 µm to 550 ± 40 µm after 3 months and 535 ± 40 µm after 6 months postoperatively. CONCLUSIONS: DMEK affects both measured corneal biomechanical properties in patients with FECD: CH and CRF. This has to be taken into account for the accuracy of intraocular pressure measurements.

Bilateral Descemet Membrane Endothelial Keratoplasty: Analysis of Clinical Outcome in First and Fellow Eye.

PURPOSE: To analyze the clinical outcomes, complications, comparability, and predictors of sequential bilateral Descemet membrane endothelial keratoplasty (DMEK). METHODS: Retrospective analyses were completed on 60 patients (120 eyes) with corneal endothelial disorders who underwent bilateral sequential DMEK. Main outcome measures were best-corrected visual acuity (BCVA), pachymetry, endothelial cell density, rebubbling frequency, and graft or nongraft-associated complications-as measured 6 and 12 months after surgery. RESULTS: BCVA, pachymetry, and endothelial cell loss did not differ significantly 6 and 12 months after surgery in first versus fellow eyes (P > 0.05, respectively). Graft and nongraft-associated complications such as graft detachment, graft failure, graft rejection, anterior chamber inflammation, and intraocular pressure decompensation did not differ significantly between first and fellow eyes (P > 0.05, respectively). The BCVA of first eyes 6 and 12 months after surgery correlates significantly with the 12-month BCVA of fellow eyes (r = 0.454, P = 0.031; r = 0.602, P = 0.001, respectively). Nevertheless, it was not possible to identify BCVA as an influencing variable on fellow eye outcome in regression modeling. Early sequential DMEK did not increase patients' risk of early immune reactions in their fellow eyes. CONCLUSIONS: The clinical outcomes of first and fellow eyes were comparable in patients after DMEK. This suggests patients will experience good fellow eye outcomes after successful first eye DMEK. When certain quality characteristics are maintained, donor differences do not significantly affect DMEK results. We found no significant correlation in postoperative complications in first and fellow eye DMEK surgeries.

Preoperative serum pattern analysis to predict the outcome of tonsillectomy in adults with chronic tonsillitis.

The method of classification and tree analysis (CART) was used to predict the outcome of tonsillectomy for chronic tonsillitis (CHT) analyzing patterns of serological markers. In a prospective case study of 24 adult patients with CHT in comparison to 24 patients with acute peritonsillar abscess (PTA) blood samples were assessed 1 day before (T-1) and 3 days after tonsillectomy. Outcome 6 months later (T180) was documented using the Glasgow Benefit Inventory (GBI) and the Specific Benefits from Tonsillectomy Inventory (SBTI). In comparison to PTA, patients with CHT were at best classified by C-reactive protein with a cut-off value of <16.735 mg/dl. For CHT, immunoglobulin E ≤ 144.65 kU/l and the combination of monocytes ≤ 0.565 Gpt/l plus leucocytes >5.855 Gpt/l at T-1 were the best classificators for higher SBTI overall score and symptom score symptom score, respectively, at T180. A higher benefit subscore at T180 was associated to γ-globulin >15.85 % plus α2-globulin >8.950% at T-1. The best classificator for better GBI overall score at T180 was an ASL titer >169.0 IU/ml or the combination of an ASL titer ≤ 169.0 IU/ml with lymphocytes ≤ 2.195 Gpt/l. Lymphocytes ≤ 2.195 Gpt/l were associated with higher GBI general subscore. Leukocytes ≤ 6.780 Gpt/l were related to higher GBI social support subscore. The combination of immunoglobulin A >1.360 g/l with procalcitonin level >0.058 ng/ml was the best combination to classify for higher physical health score. Instead of looking on isolated serologic markers, CART of multiple parameters seems to be more effective to predict the outcome of tonsillectomy for CHT.

Clinical significance and diagnostic usefulness of serologic markers for improvement of outcome of tonsillectomy in adults with chronic tonsillitis.

BACKGROUND: The aim of the present study was to explore serological biomarkers which predict the outcome of tonsillectomy for chronic tonsillitis. METHODS: A case study in a University ENT department of 24 adult patients with chronic tonsillitis (CHT) in comparison to 24 patients with acute peritonsillar abscess (PTA) was performed. Blood samples for clinical routine hematological and serological parameters were assessed prior to surgery (T-1) and five days (T5) after tonsillectomy. Outcome 6 months later (T180) was documented using the Glasgow Benefit Inventory (GBI) and the Specific Benefits from Tonsillectomy Inventory (SBTI). Correlation analyses between CHT and PTA group as well as between the different time points within each group concerning the serological parameters and the outcome parameters were performed. RESULTS: At T-1, patients in the CHT group presented with significantly higher lymphocytes counts (relative and absolute), basophils (relative and absolute) and eosinophils but less white-cells, monocytes, neutrophils (absolute and relative), alpha-1, alpha-2, beta globulins, immunoglobulin and lower C-reactive protein and procalcitonin values than patients in the PTA group (all p < 0.05, respectively). Within each group, different significant changes of the serum parameters (often in opposite direction) were observed between T-1 and T5. SBTI scores at T-1 were significantly lower in the CHT group. In contrast, most GBI scores at T180 were significantly higher in the CHT group. Between T-1 and T180 the SBTI scores improved in three quarters of the CHT patients but only in three fifths of the PTA patients. Higher eosinophil counts and immunoglobulin E levels at T-1 predicted higher GBI scores at T180 in the CHT group. CONCLUSIONS: This pilot study showed a specific serological pattern for patients with chronic tonsillitis with a specific pattern of changes after tonsillectomy. But there is no established role for biomarkers currently used in clinical practice to predict the outcome of tonsillectomy for chronic tonsillitis.