The "triple-layer sign": an optical coherence tomography signature for the detection of non-exudative macular neovascularization.

PURPOSE: To assess the sensitivity and specificity of the "triple layer sign" (TLS) (retinal pigment epithelium (RPE), neovascular tissue, and Bruch's membrane) on structural optical coherence tomography (OCT) images for the diagnosis of treatment-naïve non-exudative type-1 macular neovascularization (NE-MNV) in age-related macular degeneration (AMD). DESIGN: Cross-sectional study. METHODS: Two masked retinal experts evaluated the presence of the TLS in eyes with NE-MNV and controls with an RPE elevation without exudation due to other causes than NE-MNV in AMD [e.g., medium-large drusen, cuticular drusen, basal laminar deposits (BlamD)]. RESULTS: 130 eyes of 98 consecutive patients met the study criteria; 40 eyes of 40 patients satisfied the criteria for being included in the NE-MNV secondary to AMD group (27 females, 13 males, with a mean age of 73.8 ± 8.0 years), and 90 eyes of 58 patients met the criteria to be included in the control group (31 eyes were included in the medium-to-large drusen sub-group, 32 eyes in the cuticular drusen sub-group, and 27 eyes in the BlamD group. The TLS was observed in 39/40 patients with NE-MNV and 8/90 controls. The sensitivity and specificity of the TLS for the diagnosis of NE-MNV were 97% and 91%, respectively. CONCLUSIONS: The TLS on OCT demonstrated high sensitivity and specificity values in detecting treatment-naive type 1 NE-MNV.

Widefield oct-angiography-based classification of sickle cell retinopathy.

PURPOSE: To assess the capillary non-perfusion in different concentric sectors on widefield optical coherence tomography angiography (WF-OCTA) and to correlate the ratio of non-perfusion (RNP) to the severity of sickle cell retinopathy (SCR). METHODS: This retrospective, cross-sectional study included eyes of patients with various sickle cell disease (SCD) genotypes having undergone WF-OCTA and ultra-widefield color fundus photography (UWF-CFP). Eyes were grouped as no SCR, non-proliferative SCR or proliferative SCR. RNP was assessed on WF-OCTA montage in different field-of-view (FOV) sectors centered on the fovea: 0-10-degrees circle excluding the foveal avascular zone, the 10-30-degrees circle excluding the optic nerve, the 30-60-degrees circle, and the full 60-degrees circle. RESULTS: Forty-two eyes of twenty-eight patients were included. Within each SCR group, mean RNP of the FOV 30-60 sector was higher than all other sectors (p < 0.05). Mean RNP of all sectors were significatively different between no SCR group and proliferative SCR group (p < 0.05). To distinguish no SCR versus non-proliferative SCR FOV 30-60 had a good sensitivity and specificity of 41.67% and 93.33%, respectively (cutoff RNP > 22.72%, AUC = 0.75, 95% CI 0.56-0.94, p = 0.028). To differentiate non-proliferative versus proliferative SCR, FOV 0-10 had good sensitivity and specificity of 33.33% and 91.67%, respectively (cutoff RNP > 18.09, AUC = 0.73, 95% CI 0.53 to 0.93, p = 0.041). To discern no SCR versus proliferative SCR, all sectors had optimal sensitivity and specificity (p < 0.05). CONCLUSION: WF OCTA-based RNP provides non-invasive diagnostic information regarding the presence and severity of SCR, and correlates with disease stage in certain FOV sectors.

PHOTOBIOMODULATION THERAPY FOR LARGE SOFT DRUSEN AND DRUSENOID PIGMENT EPITHELIAL DETACHMENT IN AGE-RELATED MACULAR DEGENERATION: A Single-Center Prospective Pilot Study.

PURPOSE: To evaluate visual acuity and morphologic changes after photobiomodulation (PBM) for patients affected with large soft drusen and/or drusenoid pigment epithelial detachment associated with dry age-related macular degeneration. METHOD: Twenty eyes with large soft drusen and/or drusenoid pigment epithelial detachment age-related macular degeneration were included and treated using the LumiThera Valeda Light Delivery System. All patients underwent two treatments per week for 5 weeks. Outcome measures included best-corrected visual acuity, microperimetry-scotopic testing, drusen volume, central drusen thickness, and quality of life score at baseline and month 6 (M6) follow-up. Data of best-corrected visual acuity, drusen volume, and central drusen thickness were also recorded at week 5 (W5). RESULTS: Best-corrected visual acuity significantly improved at M6 with a mean score gain of 5.5 letters ( P = 0.007). Retinal sensitivity decreased by 0.1 dB ( P = 0.17). The mean fixation stability increased by 0.45% ( P = 0.72). Drusen volume decreased by 0.11 mm 3 ( P = 0.03). Central drusen thickness was reduced by a mean of 17.05 µ m ( P = 0.01). Geographic atrophy area increased by 0.06 mm 2 ( P = 0.01) over a 6-month follow-up, and quality of life score increased by 3,07 points on average ( P = 0.05). One patient presented a drusenoid pigment epithelial detachment rupture at M6 after PBM treatment. CONCLUSION: The visual and anatomical improvements in our patients support previous reports on PBM. PBM may provide a valid therapeutic option for large soft drusen and drusenoid pigment epithelial detachment age-related macular degeneration and may potentially slow the natural course of the disease.

SUBRETINAL TRANSIENT HYPOREFLECTIVITY IN AGE-RELATED MACULAR DEGENERATION: A Spectral Domain Optical Coherence Tomography Study.

PURPOSE: To describe and assess the prognostic significance of subretinal transient hyporeflectivity (STHR) on a novel spectral domain optical coherence tomography (SD-OCT) in age-related macular degeneration. METHODS: Consecutive patients with age-related macular degeneration (AMD) presenting STHR, defined as a small, well-defined, round subretinal, hyporeflective lesion, on SD-OCT and without exudative signs were included. Clinical examination and SD-OCT (SPECTRALIS, Heidelberg Engineering, Heidelberg, Germany) were analyzed at inclusion, 1 month before inclusion, and until the onset of exudative signs during the 12-month follow-up. RESULTS: Thirty-five STHR in 21 eyes of 20 patients were included. Among the 21 eyes, 2 eyes had early AMD, 1 eye had nonexudative asymptomatic macular neovascularization, and 18 eyes presented late AMD: 17 eyes neovascular AMD and 1 eye geographic atrophy. During the 2-month follow-up, 97.1% (34/35) of STHR disappeared. During the 12-month follow-up, 57.1% of eyes (12/21) developed exudative signs on 1 eye with early AMD and 11 eyes with neovascular AMD. CONCLUSION: Subretinal transient hyporeflectivity is a novel SD-OCT sign in patients with AMD. The eyes with isolated STHR should be closely monitored on a monthly basis to detect further exudation.

FOCAL CHOROIDAL THICKNESS HEMODYNAMICS AS a SIGN OF MACULAR NEOVASCULARIZATION ACTIVITY IN PATHOLOGIC MYOPIA.

PURPOSE: To analyze the relationship between a focal increase of choroidal thickness (ChT) and exudative activity of macular neovascularization (MNV) secondary to pathologic myopia. METHODS: Retrospective analysis including eyes with pathologic myopia presenting with a focally increased ChT underneath active MNV. All patients included were treated, and ChT was measured before and after each intravitreal injection by two experienced ophthalmologists. RESULTS: Fifty-two eyes of 52 patients with myopic MNV (19 men and 33 women) were included in this analysis. ChT at T-1 averaged 51.09 ± 33.56 µ m, whereas at the time of MNV activation (T0), ChT was significantly thicker: 85.11 ± 43.99 µ m ( P < 0.001). After a single intravitreal injection, the ChT significantly decreased to 53.23 ± 34.15 µ m ( P < 0.001). CONCLUSION: This study showed that focal ChT variations may be considered an interesting corollary sign of MNV in high myopic patients, indicating the activity of myopic neovascularization.

Undetectable Macular Neovascularization on OCT Angiography in Age Related Macular Degeneration: Comparison between Different Devices.

Background and Objectives: The aim of this study was to report the characteristics of macular neovascularization (MNV) with undetectable flow on optical coherence tomography angiography (OCTA) in neovascular age related macular degeneration (nAMD), and compare them with the characteristics of detectable MNV. Materials and Methods: Patients with a diagnosis of nAMD who underwent dye imaging and OCTA in the same day were included and divided into two groups: undetectable and detectable flow on OCTA. Three OCTA devices were used, two with spectral-domain technology (AngioVue, RTVue 100xAvanti, Optovue, Freemont, CA, USA and Heidelberg OCT2 Beta Angiography Module, Heidelberg Engineering, Germany) and one swept-source OCTA (PlexElite 9000; Carl Zeiss Meditec, Inc., Dublin, CA, USA). We studied the demographics, neovascularization characteristics, and OCTA device and acquisition characteristics for both groups. Results: A global comparison between Group 1 and Group 2 was made, followed by an analysis of variables associated with (un)detectability for each OCTA device. A total of 108 eyes were included: 90 in the detectable group (Group 1) and 18 in the undetectable group (Group 2), corresponding to a global sensitivity of OCTA for the detection of MNV of 83.49%. There was a statistically significant difference between the two groups regarding MNV type (p = 0.02) and PED height (p = 0.017). For the three devices, detection sensitivity with automatic segmentation was significantly lower than with manual segmentation. For Heidelberg, PED Height and scan quality explained 68.3% of the undetectability. For AngioVue, PED Height and absence of hemorrhage explained 67.9% of undetectability. Conclusions: In this study, we found a global sensitivity of 83.49% for the three OCTA devices combined, with a range from 55.5% to 96.26% depending on the segmentation and OCTA device. This means that undetectable/undetected MNV can represent up to 45% of the examinations, eventually misdiagnosing choroidal neovascularization for 1 out every 2 patients.

INTRARETINAL HYPERREFLECTIVE LINES.

PURPOSE: To report intraretinal hyperreflective lines related to various macular conditions. METHODS: All cases were imaged with color photographs, autofluorescence images, and spectral-domain optical coherence tomography, some with fluorescein and/or indocyanine green angiography. Demographic data, imaging, course and outcome were retrospectively analyzed. RESULTS: Forty-nine eyes of 43 patients (16 men and 27 women) were included. Hyperreflective vertical lines (38 eyes) or curvilinear lines along the Henle fiber layer (11 eyes) were present in association with various macular conditions: adult vitelliform dystrophy or pattern dystrophy (24 eyes) frequently associated with an epiretinal membrane (six eyes) and/or thick choroid (nine eyes), age-related maculopathy or macular degeneration (nine eyes), partial resorption of subretinal or intraretinal hemorrhages (five eyes), idiopathic macular microhole (two eyes), vitreomacular traction (three eyes), multiple evanescent white dot syndrome (three eyes), fundus flavimaculatus (two eyes), and pachychoroid pigment epitheliopathy (one eye). The lines fully vanished in cases of hemorrhages, multiple evanescent white dot syndrome or resolution of vitreomacular traction, but usually persisted with gradual thinning in the other conditions. CONCLUSION: The present series showed that intraretinal hyperreflective lines could occur in various inflammatory, degenerative, or tractional conditions. They could reflect a previously unrecognized reaction to various photoreceptor, Müller cell, and/or retinal pigment epithelium damage.

CHORIOCAPILLARIS FLOW IMPAIRMENT IN TYPE 3 MACULAR NEOVASCULARIZATION: A Quantitative Analysis Using Swept-Source Optical Coherence Tomography Angiography.

PURPOSE: To quantitatively analyze choriocapillaris alterations using swept-source optical coherence tomography angiography in eyes presenting with Type 3 macular neovascularization (MNV) and to compare these alterations with eyes presenting with intermediate AMD (iAMD). METHODS: Macular 3 × 3-mm swept-source optical coherence tomography angiography scans were retrospectively analyzed in eyes with Type 3 MNV and in eyes with iAMD. The choriocapillaris en face slabs were extracted from the swept-source optical coherence tomography angiography device after manual segmentation. En face choriocapillaris flow images were compensated with en face choriocapillaris structure images, followed by the Phansalkar local thresholding method using a window radius of 4 and 8 pixels. The percentage of flow deficits (FD%), the number, size, and total area of FDs were computed for comparison. A secondary analysis was performed in the four corners of the image to include equidistant regions in all eyes. RESULTS: Twenty-six Type 3 MNV eyes of 21 patients and 26 iAMD eyes of 17 patients were included. Compared with iAMD eyes, eyes with Type 3 MNV displayed a higher FD% (41.37% ± 14.74 vs. 19.80% ± 9.63 using radius 4 pixels [P < 0.001]; 45.24% ± 11.9 vs. 26.63% ± 8.96 using radius 8 pixels [P < 0.001]). The average size of FDs was significantly larger in Type 3 MNV eyes compared with iAMD eyes (P < 0.001), whereas the number of FDs was significantly lower in Type 3 MNV compared with iAMD eyes (P < 0.001). CONCLUSION: Type 3 MNV eyes present with increased choriocapillaris flow impairment compared with iAMD eyes. Reduced choriocapillaris perfusion may contribute to Type 3 MNV development and pathogenesis.

SUB-RETINAL PIGMENT EPITHELIUM MULTILAMINAR HYPERREFLECTIVITY AT THE ONSET OF TYPE 3 MACULAR NEOVASCULARIZATION.

PURPOSE: To report the prevalence and treatment outcomes of eyes with sub-retinal pigment epithelium (sub-RPE) multilaminar hyperreflectivity at the onset/clinical detection of Type 3 macular neovascularization (MNV) secondary to exudative age-related macular degeneration. METHODS: Retrospective analysis of consecutive patients diagnosed with Type 3 MNV secondary to age-related macular degeneration was performed. Eyes presenting with sub-RPE multilaminar hyperreflectivity on structural optical coherence tomography at the onset of Type 3 MNV were included in this study. An age-, sex-, and stage-matched control group was composed of eyes affected by Type 3 MNV without sub-RPE multilaminar hyperreflectivity. Prevalence and treatment outcomes after anti-vascular endothelial growth factor injections at 1-year follow-up were analyzed in both groups. RESULTS: Nineteen treatment-naïve eyes of 19 patients (8 men/11 women, mean age 83 ± 8 years old) presenting with sub-RPE multilaminar hyperreflectivity before or at the onset/clinical detection of Type 3 MNV were included from a cohort of 162 eyes with treatment-naïve Type 3 MNV. This accounts for an estimated prevalence of 11.7% (5.8-15.2, 95% confidence intervals). No significant differences were disclosed between cases studied and the control group (143 eyes of 143 patients) in age, sex, best-corrected visual acuity at baseline, and number of injections. Best-corrected visual acuity did not improve during the 1-year follow-up in patients showing sub-RPE multilaminar hyperreflectivity (P = 0.45), whereas best-corrected visual acuity significantly increased in the control group (P < 0.001). The presence of sub-RPE multilaminar hyperreflectivity in the context of Type 3 MNV was significantly associated with regressive calcific drusen (P < 0.001) and multiple Type 3 lesions/eye (P < 0.001). CONCLUSION: The detection of multilaminar hyperreflectivity at the onset/clinical detection of Type 3 MNV suggests that chronic exudation (i.e., the "onion-sign") in the sub-RPE space (i.e., focal sub-RPE neovascularization) may precede the onset/clinical detection of Type 3 MNV. Sub-retinal pigment epithelium multilaminar hyperreflectivity at the onset of Type 3 MNV may be an important predictor of poor visual outcome in these eyes.

Multimodal imaging of bilateral ischemic retinal vasculopathy associated with Berger's IgA nephropathy: case report.

BACKGROUND: Berger's IgA nephropathy (IgAN) is the most common primary glomerulonephritis. However, some rare cases of retinal manifestations have been described, with only two cases of retinal vasculopathy reported in the literature. Here we report an uncommon case of bilateral ischemic retinal vasculopathy associated with Berger IgAN, evaluated with complete multimodal imaging including ultra-wide field (UWF) imaging and swept source optical coherence tomography angiography (SS-OCTA). CASE PRESENTATION: A 51-year-old woman with a history of Berger's IgA nephropathy complained of visual impairment in both eyes. Fundus examination showed bilateral peripapillary arterial attenuation and perivascular sheathing, associated to perifoveal telangiectatic lesions. There was a central scotoma in the perimetry of the right eye and peripheral visual field defect in the left eye. Full-field electroretinogram revealed significantly reduced oscillatory potentials. Spectral domain optical coherence tomography showed multiple focal areas of thinning of the inner retina, indicating long-lasting vascular occlusion lesions. UWF fluorescein angiography showed the presence of bilateral vasculitis, diffuse capillary leakage, macular ischemia and telangiectasia. SS-OCTA better highlighted the macular ischemia and vascular anomalies layer-by-layer. CONCLUSIONS: Retinal vasculopathy is a very rare condition observed in IgA nephropathy. To our knowledge, this is the first report of complete multimodal functional and structural imaging. UWF imaging was very useful for accurate and comprehensive disease assessment, and OCTA was able to assess posterior pole vascular lesions.

Optical Coherence Tomography Angiography in Optic Nerve Drusen.

AIM: To determine the efficacy of optical coherence tomography angiography (OCT-A) in diagnosing optic nerve head flow impairment in patients with optic nerve drusen. METHODS: Patients affected by optic-nerve head drusen (ONHD) attending the Eye Clinic of the Federico II University of Naples were enrolled in this prospective case series between October 2015 and October 2016. Each patient underwent evaluation of best corrected visual acuity (BCVA), Goldman applanation tonometry, slit-lamp biomicroscopy, fundus examination, standard visual-field testing (perimetry), spectral domain (SD)-OCT and OCT-A. RESULTS: Thirteen patients (6 females and 7 males with a mean age of 22.05 ± 7.54 years) with ONHD (19 eyes) were enrolled. Mean BCVA was 0.16 ± 0.21 LogMar and mean intraocular pressure was 15.68 ± 1.66 mm Hg. The control group constituted 16 individuals (24 eyes). Both ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL) parameters were lower in patients than in controls. Similarly, the flow index (U = 134, p = 0.021) and vessel density (U = 90, p = 0.001) were significantly lower in eyes affected by ONHD than in normal eyes. Visual-field parameters did not differ between the 2 groups. GCC parameters were significantly correlated with OCT-A parameters (p < 0.05). No correlation was found between RNFL and OCT-A parameters. CONCLUSIONS: Our data suggest that OCT-A could be an objective method, helpful in the analysis of flow changes in patients with ONHD.

Intraretinal changes in the presence of epiretinal traction.

BACKGROUND: To determine the correlation between the area of morphological changes on the macular surface, the depth of intraretinal changes and the best-corrected visual acuity (BCVA) in patients with idiopathic epiretinal membrane. METHODS: In this prospective cross-sectional study, 38 patients underwent BCVA testing with a Snellen eye chart. The depth of traction, photoreceptor outer segment layer (PROS) thickness, central macular thickness (CMT) and presence of intraretinal cysts were measured using the Avanti RTVue XR and 3D Widefield Enface OCT instruments. Enface sections were performed at the inner limiting membrane (ILM) line level (ILM offset). Patients were categorized into two groups: in group 1 (n = 21), the depth of traction was within 90 µm from the ILM, and in group 2 (n = 17) it was beyond 90 µm from the ILM. The main outcome measure was the correlation between area of epiretinal traction and BCVA according to the depth of traction. RESULTS: In group 1, the depth of traction was 55.15 ± 14.28 µm, the area of traction was 38.95 ± 13.63 mm2, PROS thickness was 51.20 ± 7.23 µm, and CMT was 362.65 ± 41.08 µm. In group 2, the depth of traction was 112.24 ± 10.89 µm, the area of traction was 25.18 ± 4.07 mm2, PROS thickness was 50.24 ± 9.01 µm, and mean CMT was 534.29 ± 126.81 µm. Statistically significant differences in depth of traction, area of traction and CMT were found between the two groups (P < 0.001). The relationship between structure and function between the area of traction and BCVA was better explained in group 2 (r = 0.814, P < 0.001). CONCLUSIONS: We found that intraretinal changes were induced by the ERM, and varied according to the depth of traction measured with en face analysis. In the case of traction deeper than 90 µm, we found a significant correlation between the inner area of the epiretinal traction and BCVA. We believe that retinal stress induced by epiretinal traction is better characterized by combining information provided by sagittal and transverse OCT scans, thus defining its prognostic significance in ERM.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY CHANGES IN EARLY TYPE 3 NEOVASCULARIZATION AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT.

PURPOSE: To investigate the morphologic changes on optical coherence tomography angiography (OCTA) of treatment-naive Type 3 neovascularization secondary to exudative age-related macular degeneration after 1 year of anti-vascular endothelial growth factor therapy. METHODS: Consecutive patients diagnosed with treatment-naive early-stage Type 3 neovascularization were enrolled in this retrospective study. All patients underwent color fundus photographs/MultiColor (Heidelberg Engineering) imaging, fluorescein angiography, indocyanine green angiography, structural spectral domain OCT, and OCTA Optovue RTVue XR Avanti (Optovue) at baseline, and repeated OCTA and structural spectral domain OCT at Month 12. Qualitative analysis of the 3 × 3 OCTA examinations at baseline and Month 12 was then compared, to assess changes after anti-vascular endothelial growth factor therapy. RESULTS: A total of 15 treatment-naive eyes of 15 consecutive patients were included in the analysis. At 12-month follow-up after pro-re-data anti-vascular endothelial growth factor therapy (5.75 ± 1.48 injections of ranibizumab, and injections of 6.33 ± 1.21 of aflibercept), OCTA demonstrated persistence of the deep capillary plexus abnormalities in 13/15 eyes. In the outer retina and choriocapillaris, the initial lesion became undetectable in 7/15 cases, accompanied by choriocapillaris atrophy. The abnormal vascular complex persisted in the form of a tuft-shaped lesion in the outer retinal segmentation in 9/15 eyes, which in the choriocapillaris segmentation was associated with sub-retinal pigment epithelium neovascularization in 8 cases. CONCLUSION: Optical coherence tomography angiography showed that the tuft-shaped abnormal outer retinal lesion, frequently associated with a small clew-like flow signal in the choriocapillaris, after 1 year of anti-vascular endothelial growth factor therapy, either becomes undetectable or develops sub-retinal pigment epithelium neovascularization.

Peripapillary hyperreflective ovoid mass-like structures and the retinal nerve fiber layer thinning.

AIM: We describe a report of three cases of bilateral Peripapillary Hyperreflective Ovoid Mass-Like Structures (PHOMS), their respective multimodal imaging, and retinal nerve fiber layer (RNFL) analysis over time. METHODS: We performed an elaborated multimodal imaging of three pediatric patients with PHOMS. We performed a visual acuity testing, followed by a biomicroscopic and fundus examination, an additional Optical Coherence Tomography (OCT), fundus autofluorescence (FAF), infra-red (IR), fluorescein angiography (FA), Scanning laser Ophtalmoscopy (SLO), and retro-mode imaging. Furthermore, we analyzed RNFL thickness over several consecutive visits. RESULTS: The multimodal approach exhibited similar characteristics of PHOMS in all eyes, namely a torus-like shaped that was particularly demarcated and well visualized using SLO and retro-mode tool. In all the eyes, we found a downward trend of the RNFL over time. In both the right and left eye, RNFL at presentation averaged at 152.33 ± 25.42 and 130 ± 18.33 microns, respectively. Several weeks after, it averaged at 142 ± 30.34 and 125.67 ± 14.84 microns, respectively. CONCLUSIONS: Our report shows a thinning trend of the RNFL thickness over time in patients with PHOMS.

Navigated Focal Laser of Macular Telangiectasia Type I (Adult-Onset Coats' Disease).

We aimed to evaluate the anatomical and functional outcome of selective photocoagulation of idiopathic macular telangiectasia type 1 by navigated focal laser (Navilas, OD-OS GmBH). Consecutive patients with idiopathic macular telangiectasia type 1 were included in the analysis. All patients were treated with navigated focal laser, planned on multimodal imaging. Seven eyes of seven patients were retrospectively analyzed. Navigated laser photocoagulation of idiopathic macular telangiectasia type 1 successfully occluded the microaneurysms, inducing regression of macular edema and exudation, significative improvement in best-corrected visual acuity at 3 (P = 0.035) and 6 months (P = 0.034) and a decrease in central macular thickness at 3 (P = 0.01) and 6 months (P = 0.01). Patients with idiopathic macular telangiectasia type 1 are ideal candidates for navigated laser treatment. Navigated focal treatment has been shown to be effective and safe in occluding aneurysmal dilations without any side effects. [Ophthalmic Surg Lasers Imaging Retina 2024;55:545-551.].