Postintravitreal Injection Endophthalmitis: Incidence, Characteristics, Management, and Outcome.

Purpose: Postintravitreal injection (IVI) endophthalmitis is a rare but devastating complication. Herein, we report the incidence ,and clinical and microbiological characteristics, as well as the visual outcome, in IVIs endophthalmitis in two medical centers. Methods: All patients undergoing intravitreal injections between 1/2018 and 12/2019 in two large medical centers were analyzed for post-IVI endophthalmitis. Results: Of the total of 51,356 IVIs performed, 23 cases of post-IVI endophthalmitis were diagnosed, yielding an overall incidence of 0.045%. The median interval from IVI to symptoms onset was 2 days (IQR: 1-5). Cultures were positive in 56% of the cases (100% Gram-positive bacteria and 76% coagulase-negative staphylococcus). Parameters associated with higher culture-positive rates included samples taken during vitrectomy, WBC on vitreous smear, the number of IVIs in the 12 months prior to presentation, and the time interval from last IVI to diagnostic sampling. At 6- and 12-month follow-up, the median change in VA (logMAR) was -1.10 (IQR: (-1.32)-(-0.40)) and -1.02 (IQR: (-1.10)-(-0.30)), respectively. Younger age and better BCVA at presentation were associated with better VA outcome, while positive culture result and systemic steroids treatment were each associated with the worse visual outcome. We found no difference in visual outcomes between PPV and TAI as a primary procedure. Conclusion: Post-IVI endophthalmitis is a rare complication, and most patients do not regain their initial VA. Certain parameters (clinical, microbiological, and therapeutic) may help anticipate the outcome and guide decision making regarding diagnosis and treatment.

Long-term outcomes of anti-vascular endothelial growth factor treatment in peripapillary choroidal neovascularisation due to age-related macular degeneration.

OBJECTIVE: To report the long-term outcomes of anti-vascular endothelial growth factor (VEGF) treatment in eyes with peripapillary choroidal neovascularisation (PPCNV) associated with age-related macular degeneration (AMD). METHODS: A retrospective cohort study included patients with AMD-related PPCNV. Eyes were treated with anti-VEGF according to pro re nata regimen. Inactivation index was calculated as the proportion of disease inactivity from the total follow up time. RESULTS: Sixty-seven eyes of 66 consecutive patients were included in the study; mean follow-up time was 53.2 months. Best corrected visual acuity (BCVA) remained stable for the first four years of follow up, with a significant deterioration in BCVA thereafter. Baseline BCVA was a significant predictor of final BCVA (p < 0.001). The mean inactivation index was 0.38 ± 0.23. Subretinal fluid (SRF) at presentation was significantly associated with decreased inactivation index (p < 0.05). Worse baseline BCVA, SRF and pigment epithelium detachment (PED), male sex, and younger patient age were associated with increased risk for recurrence after first inactivation (p < 0.05). CONCLUSION: The use of anti-VEGF agents in the treatment of AMD-related PPCNV managed to preserve BCVA in the first four years of follow-up. Male sex, SRF and PED at presentation and baseline BCVA are associated with increased risk for PPCNV recurrence after the first inactivation, and should prompt careful follow-up in these patients.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IMAGING OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO CHOROIDAL RUPTURE TREATED BY INTRAVITREAL RANIBIZUMAB.

PURPOSE: To describe optical coherence tomography angiography findings at baseline and during the follow-up of choroidal neovascularization secondary to choroidal rupture (CR) in a patient with kidney transplant treated by a single intravitreal injection of ranibizumab. METHODS: The clinical course, conventional multimodal imaging findings including ultra-widefield fundus color photography and fundus autofluorescence (Optos California, Marlborough, MA), spectral-domain optical coherence tomography (SD-OCT Spectralis; Heidelberg Engineering, Heidelberg, Germany), fluorescein angiography (FA; Heidelberg Engineering, Heidelberg, Germany), indocyanine green angiography ,and optical coherence tomography angiography (Plex-Elite, Carl Zeiss Meditec, Inc, Dublin, CA) findings at baseline and during the follow-up of a patient with choroidal neovascularization secondary to CR. RESULTS: A 19-year-old young man with a history of blunt trauma presented with acute visual decline of the right eye. He had a systemic history of kidney transplant. His best-corrected visual acuity was 20/200 in the right eye and 20/20 in the left eye at baseline. Funduscopic examination and ultra-widefield fundus autofluorescence imaging revealed a double vertical macular lesion corresponding to a CR in the right eye. Spectral-domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography revealed active Type 2 choroidal neovascularization secondary to the CR. Optical coherence tomography angiography showed a high-flow neovascular network consistent with conventional multimodal imaging. One month after intravitreal injection of ranibizumab, bestcorrected visual acuity was 20/100, optical coherence tomography angiography showed a contraction and remodeling of the neovascular flow, and exudative signs disappeared on multimodal imaging. No side effect was detected. CONCLUSION: Optical coherence tomography angiography is able to detect choroidal neovascularization secondary to CR at baseline and during the follow-up after a single intravitreal injection of ranibizumab. Ranibizumab was effective in the treatment of this sight-threatening lesion in a patient with a history of kidney transplant.

A Modified Surgical Technique for Submacular Injection.

BACKGROUND AND OBJECTIVE: To describe a modified simple surgical technique for submacular injection. PATIENTS AND METHODS: The technique involves pars plana vitrectomy, a viscous fluid control (VFC) system for semi-automatic subretinal injection of tissue plasminogen activator (tPA), bevacizumab, and air and intravitreal gas injection for submacular hemorrhage (SMH), or subretinal balanced salt solution (BSS) for submacular perfluorocarbon (PFC) bubbles or persistent macular holes. RESULTS: This technique was successfully performed for SMH (five patients), a subfoveal PFC bubble (two patients), and persistent full-thickness macular hole (FTMH) (one patient). The single surgical complication was an FTMH in a PFC bubble. Four SMH patients had postoperative displacement of the hemorrhage. The FTMH was partially closed. CONCLUSIONS: Semi-automatic subretinal injection of tPA, bevacizumab, and air with the VFC system promoted displacement and clearance of SMH without complications. A subretinal BSS injection is effective for removing subfoveal PFC bubbles and for closing persistent FTMH. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:551-555.].

Spectral-Domain Optical Coherence Tomography Analysis of Fibrotic Lesions in Neovascular Age-Related Macular Degeneration.

PURPOSE: To describe the spectral-domain optical coherence tomography (OCT) features of fibrotic lesions associated with neovascular age-related macular degeneration (nAMD) and to outline the progression pathways from initial macular choroidal neovascular lesions (CNVs) to fibrosis. METHODS: Patients with nAMD were retrospectively included when macular subretinal fibrosis was present. Fibrosis was categorized using spectral-domain OCT with respect to retinal pigment epithelium (RPE) in 836 spectral-domain OCT slices from 44 eyes of 39 patients. In addition, in 47 distinct eyes, 4181 spectral-domain OCT slices were retrospectively reviewed to longitudinally assess progression from the initial lesion to the final fibrosis. RESULTS: Cross-sectional analysis classified fibrosis on spectral-domain OCT slices, as type A if located underneath the RPE, as type B if located above the RPE, and as type C if the remaining RPE was undistinguishable. The longitudinal analysis series revealed 3 progression pathways from the original CNV: 1) progression to type A, followed by RPE erosion and subretinal hyperreflective material, then type B and type C fibroglial lesion (FGL; 17/47 eyes); 2) progression to type B then type C FGL (17/47 eyes); and 3) persistence of type A with development of a flat, fibroatrophic lesion (13/47 eyes). Subretinal hyperreflective material, macular hemorrhage, or RPE tear occurred in 14 of 47, 13 of 47, and 10 of 47 eyes, respectively. CONCLUSION: This spectral-domain OCT analysis identified various patterns of macular fibrosis in eyes with nAMD. Three pathways of progression to fibrosis were described including the well-established pathway of type 2 CNV progression to FGL and the progression of type 1 fibrovascular CNV to FGL or fibroatrophic lesion.

A Two-Port Inexpensive and Effective Method for Silicone Oil Removal.

BACKGROUND: There are several ways to remove silicone oil (SO) from the vitreous cavity. OBJECTIVES: To describe a simple, safe and inexpensive method of 2-port SO removal. METHODS: Medical charts of 33 patients who underwent SO removal combined with cataract extraction were retrospectively reviewed, from a cohort of 119 patients who had silicone oil removal. The primary outcome was the rate of re-detachment, secondary outcomes included visual acuity (VA) and intraoperative and postoperative complications. RESULTS: Mean follow-up time was 27.6 months (0.25-147 ± 33.1), and mean tamponade duration prior to SO removal was 16.77 months (4-51.5 ± 14.6). The re-detachment rate was 3% (one patient). Postoperatively, seven patients (20%) had epiretinal membrane (ERM), eight patients had posterior capsule opacification (24%), and proliferative vitreoretinopathy (PVR) was diagnosed in two patients (6%). Compared to the mean VA (logarithm of the minimum angle of resolution [LogMAR]) at the preoperative examination, the mean VA (LogMAR) improved significantly at the last visit when including all ranges of VA (n=32, LogMAR 1.52 vs. 1.05 P = 0.0002 [Student's t-test] and P = 0.001 [Wilcoxon test]). CONCLUSIONS: The technique described is fast and simple, keeping the posterior capsule intact in pseudophakic patients, which is advantageous in the event of future re-detachment necessitating SO reinjection. Rates of re-detachment and postoperative ERM and PVR were low. Furthermore, our method does not require the use of a surgical microscope with posterior segment viewing systems, or opening a full disposable vitrectomy set, thus drastically reducing the procedure's cost.

REAL-COLOR VERSUS PSEUDO-COLOR IMAGING OF FIBROTIC SCARS IN EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To compare the morphological characteristics of subretinal fibrosis in late age-related macular degeneration using multicolor (MC) imaging, color fundus photography (CFP), and ultra-widefield CFP (UWFCFP). METHODS: Thirty-two eyes of 31 patients diagnosed with subretinal fibrosis complicating exudative age-related macular degeneration were included. Included eyes were imaged by MC, CFP, and UWFCFP. The overall ability to visualize fibrosis, its margins, and dissimilarity with surrounding atrophy was graded using a score (0: not visible, 1: barely visible, 2: mostly visible, and 3: fully visible) by two readers. Area of fibrosis was calculated. Scaling, lesion colocalization on all three imaging techniques, and area measurements were performed using ImageJ. RESULTS: Ninety-six images of 32 eyes were graded. The average area of fibrosis was 14.59 ± 8.94 mm for MC, 13.84 ± 8.56 mm for CFP, and 13.76 ± 8.79 mm for UWFCFP. Fibrosis was fully visible in 87.5% of cases using MC and 50% using CFP and UWFCFP. Fibrosis' margins were sharply defined in 40.6% of eyes with MC, 15.6% and 9.4% with CFP and UWFCFP, respectively. Multicolor imaging provided superior distinction between fibrosis and atrophy (100% for MC vs. 13.4% for CFP and 33.3% for UWFCFP). The inter- and intra-reader agreement was high for all measurements (P < 0.0001). CONCLUSION: Multicolor technology allows for improved visualization and analysis of subretinal fibrosis when compared with CFP and UWFCFP, especially when surrounding atrophy is present.

CHOROIDAL NEOVASCULAR AREA AND VESSEL DENSITY COMPARISON BETWEEN TWO SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY DEVICES.

PURPOSE: To compare choroidal neovascularization (CNV) area and vessel density (VD) measurements between two different swept-source optical coherence tomography angiography (SS-OCTA) devices. METHODS: En face optical coherence tomography angiography (OCTA) images of patients affected by neovascular age-related macular degeneration were collected prospectively from two devices: Zeiss PLEX Elite 9000 (Carl Zeiss Meditec, Dublin, CA) and Topcon DRI OCT Triton SS-OCTA (Topcon, Tokyo, Japan). Choroidal neovascularization area and VD of images were measured and analyzed with ImageJ software by two readers to evaluate the agreement between two devices, with respect to different image size (3 × 3 and 6 × 6 mm) and different image segmentation (automatic vs. manual), and a Topcon equivalent Zeiss segmentation as control (i.e., the equivalent anatomical slab given by Topcon device on the Zeiss device). RESULTS: A total of 30 eyes (30 patients) were analyzed. There was an excellent agreement between the two readers in CNV area measurements intraclass correlation coefficient >0.9 in all analyses. We found excellent agreement in CNV area measurements (manual and automatic segmentations) when comparing 3 × 3-mm or 6 × 6-mm images both for each single device and between the two devices (overall intraclass correlation coefficient > 0.9). Vessel density measurements between manual to automatic segmentation within the same device and same image size had a high intraclass correlation coefficient value, but there was a poor agreement in VD between different image sizes (3 × 3 mm vs. 6 × 6 mm) in the same device and also comparing the two devices (3 × 3 Topcon vs. 3 × 3 Zeiss; 6 × 6 Topcon vs. 6 × 6 Zeiss). There was a poor agreement between the Topcon equivalent Zeiss segmentation and all other segmentations. CONCLUSION: There was an excellent agreement in CNV area measurements for both swept-source optical coherence tomography angiography devices in automatic and manual segmentations. However, the Topcon equivalent Zeiss segmentation was not comparable with any of the preset segmentations of Topcon and Zeiss devices. There was a poor agreement in CNV VD between different image size and different devices. For these reasons, it seems that, for accurate longitudinal analysis of VD, it is better to use the same device for each individual, even if both devices can be used interchangeably for CNV area measurements using automatic or manual segmentations.

Subretinal pigment epithelium fibrotic tissue morphological changes after a single anti-vascular endothelial growth factor injection in age-related macular degeneration.

AIMS: To demonstrate and evaluate the morphological changes of multilayered fibrovascular pigment epithelial detachment (PED) to a single anti-vascular endothelial growth factor (VEGF) injection in age-related macular degeneration (AMD). METHODS: We retrospectively analysed the morphological changes of 30 eyes with exudative AMD showing fibrotic multilayered PED, between two consecutive visits. All patients had one anti-VEGF intravitreal injection at the first visit. We quantitatively analysed the different compartments within the PED and their morphological response. RESULTS: The mean follow-up time interval between the first and the second visit was 32.46±4.64 days. We defined three optical coherence tomography zones within the PED: a subretinal pigment epithelium inhomogeneous hyporeflective space (layer 1), a hyper-reflective band beneath layer 1 (layer 2), and a hyporeflective space between the Bruch's membrane and layer 2 (layer 3). The mean height of layer 1 was 142±44.63 and 99.30±39.79 µm at visits 1 and 2, respectively. The mean thickness of layer 2 was 101.42±46.66 and 82.76±35.24 µm at visits 1 and 2, respectively. The mean height of layer 3 was 35.77±32.77 and 5.66±8.68 µm at visits 1 and 2, respectively (p=0.009). The mean height change for layer 1 was statistically significantly higher than for layer 2 (p=0.0002). CONCLUSIONS: Fibrovascular PED was compartmented into three layers with different reflectivities that morphologically responded differently to a single anti-VEGF injection. Layer 2 had a statistically significantly lower response compared with layer 1, suggesting the hypothesis of a fibrotic component in layer 2.

Reliability and Reproducibility of Pigment Epithelial Detachment Volume Measurements in AMD Using a New Tool: ReVAnalyzer.

BACKGROUND AND OBJECTIVE: To describe and present the reliability and reproducibility of a new software, Retinal Volume Analyzer (ReVAnalyzer), for pigment epithelium detachment (PED) volume quantification. PATIENTS AND METHODS: This is a retrospective study including patients with PEDs secondary to exudative age-related macular degeneration (AMD). Macular volume scans on spectral-domain optical coherence tomography on enhanced depth imaging mode were performed in all eyes. Image batches were then exported in .xml format to the ReVAnalyzer software. A semiautomated PED volume measurement was performed by three independent readers (RBG, VC, OS) twice, at the beginning and end of a 15-day period. Bland-Altman assessment for agreement was used to compare intra- and interobserver observations. RESULTS: Twenty eyes of 20 patients presenting with PED were analyzed. Bland-Altman analysis indicated a good agreement between inter- and intraobserver measurements. The intraclass correlation coefficient for intraobserver PED volume measurements and between the three observers (interobserver) was greater than 0.99, demonstrating high reproducibility and consistency of the methodology. CONCLUSIONS: ReVAnalyzer is a reliable tool that can assist in the analysis of PED volume with high reproducibility. This type of specific retinal volume analysis can be of help for monitoring disease activity and therapeutic response in AMD. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e242-e249.].

Spontaneous closure of bilateral macular holes.

PURPOSE: To present a case of a right eye spontaneous closure of a full thickness macular hole (FTMH), followed several years later by a left eye spontaneous closure of a FTMH, in an otherwise healthy woman. OBSERVATIONS: We show the temporal changes and spontaneous resolution observed with Spectral-Domain Ocular Coherence Tomography (SD-OCT) of a FTMH in the right eye and a FTMH secondary to vitreomacular traction in the left eye of the same patient 5 years later, also with full spontaneous resolution. Following the resolution, SD-OCT demonstrated outer retinal layer disruption recovery and visual acuity improvement in both eyes. CONCLUSIONS AND IMPORTANCE: Spontaneous closure of macular holes is an uncommon event, with most descriptions in the literature being of single cases or very small series, including several reports in patients who have undergone vitrectomy for other causes, or in highly myopic eyes. Bilateral spontaneous closure of macular holes in the same patient is an even more uncommon event, described only once in one patient previously in the literature to our knowledge.

Design, fabrication, and characterization of circular Dammann gratings based on grayscale lithography.

We describe the design, fabrication, and experimental demonstration of a circular Dammann grating element generating a point-spread function of two concentric rings with equal intensity. The element was fabricated using grayscale lithography, providing a smooth and accurate phase profile. As a result, we obtained high diffraction efficiency and good uniformity between the two rings.