InCASEOf scoring system for distinction between pachychoroid-associated macular neovascularization and neovascular age-related macular degeneration in patients older than 50 years.

To develop a novel scoring system aiming at guiding the differential diagnosis between macular neovascularization secondary to pachychoroid disease (pMNV) and neovascular age-related macular degeneration (AMD) in patients aged 50 years and older. In this retrospective study performed at University Vita-Salute San Raffaele (Milan, Italy) and Créteil University Eye Clinic (Créteil, France), we enrolled patients 50 years of age and older, visited between January 2017 and January 2019, who were diagnosed with either treatment-naïve pMNV or neovascular AMD. At the time of diagnosis, all patients underwent a comprehensive ophthalmologic evaluation, spectral-domain optical coherence tomography, fluorescein angiography, indocyanine green angiography, and optical coherence tomography angiography. Univariate comparison between pMNV and neovascular AMD groups was performed to identify the main clinical predictors for pMNV. The selected predictors were taken into a binomial logistic regression and eventually served as the basis for the development of InCASEOf scoring system. Receiver operating characteristic (ROC) curves were used to study the model performance. Forty-eight right eyes from 48 patients with pMNV and 39 right eyes from 39 patients with neovascular AMD were considered in this study. Age (+ 2 points), sex (+ 2 points), choroidal thickness (+ 2 points), early pachyvessels (+ 2 points), and evidence of MNV at OCTA (+ 3 points) turned out to be predictors for pMNV. Four additional factors significant at univariate analysis were considered: type 2 and type 3 MNVs and presence of intraretinal fluid (- 0.5 points each), and presence of subretinal fluid (+ 0.5 points). InCASEOf scoring system was built with a high score of 11.5 points. The cutoff value of 6.5 showed good accuracy in separating pMNVs from neovascular AMDs. InCASEOf is a straightforward clinical scoring system, accessible to comprehensive ophthalmologists, with the purpose of enabling easy distinction and expert-like diagnosis of pMNV and neovascular AMD in patients aged 50 years or older.

Navigated micropulse laser for central serous chorioretinopathy: Efficacy, safety, and predictive factors of treatment response.

PURPOSE: There is no widely accepted treatment for persistent/chronic central serous chorioretinopathy. The present study aimed to evaluate the efficacy, safety, and factors associated to treatment response to navigated micropulse laser in chorioretinopathy. METHODS: Retrospective observational case series including consecutive patients presenting with symptomatic persistent and chronic chorioretinopathy. All patients were treated with 5% navigated micropulse laser with the Navilas system (Navilas®, OD-OS GmBH, Teltwo, Germany), by overlying fluorescein angiography, indocyanine green angiography and/or spectral domain-optical coherence tomography images of visible leaking points and/or choroidal hyperpermeability/subretinal fluid to plan the laser treatment. RESULTS: Thirty-nine eyes of 36 consecutive patients (29 men and 7 women, with a mean age of 51.87 years) were included. Logarithm of the minimum angle of resolution (LogMar) best-corrected visual acuity increased from 0.39 ± 0.24 at baseline to 0.24 ± 0.22 at 3 months (p < 0.0001) and to 0.20 ± 0.07 at 6 months (p < 0.0001). Subretinal fluid decreased from 166.82 ± 111.11 micron at baseline to 52.33 ± 78.97 micron (p < 0.0001) at 3 months and 34.12 ± 67.56 micron at 6 months (p < 0.0001). The presence of a hot spot on fluorescein angiography and a focal choroidal hyperpermeability on indocyanine green angiography, but not the duration of symptoms correlated significantly with the resolution of subretinal fluid at month 3 (p = 0.023 and p = 0.001). CONCLUSION: Navigated micropulse laser laser treatment was found to be effective and safe for the treatment of chorioretinopathy, with significant improvement in visual and anatomical outcomes, unaccompanied by any adverse event at 3 and 6 months follow-up. Factors associated to subretinal fluid resolution may allow a better selection of likely responders to navigated micropulse laser treatment.

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.

TWO-YEAR FOLLOW-UP OF A RETINAL ASTROCYTIC HAMARTOMA IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To report a case of retinal astrocytic hamartoma imaged by optical coherence tomography angiography (OCTA), followed for 2 years. METHODS: Observational case report. RESULTS: A 25-year-old woman was referred for an incidental retinal lesion in the left eye (LE). At baseline, the best-corrected visual acuity in the LE was 20/32, and fundus examination showed the presence of a round, pigmented lesion in juxtafoveal region, corresponding, on spectral domain OCT, to a hyperreflective lesion within nerve fiber layer. Optical coherence tomography angiography revealed the presence of a high-flow lesion in the superficial capillary plexus segmentation. The patient was followed up for 2 years: best-corrected visual acuity remained stable and multimodal imaging, including OCTA, confirmed the benign and stable nature of the lesion. At baseline, the total lesion area on OCTA (superficial capillary plexus) was 0.181 mm2, whereas vascular density was 52.080%; the total area was 0.204 mm2, and vascular density was 53.740% at 2-year follow-up. CONCLUSION: Optical coherence tomography angiography is helpful not only for the diagnosis and follow-up of such rare tumors, but also it gives insights as to how these tumors develop and how they affect surrounding structures.

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.

OCTA-guided navigated laser therapy for advanced macula neovascularization secondary to age related macular degeneration.

INTRODUCTION: To evaluate the effects of the Navilas system guided by optical coherence tomography angiography for advanced macular neovascularization (MNV) secondary to age-related macular degeneration (AMD). METHODS: Prospective case-series including nine eyes presenting with advanced MNV with persistence of exudative signs, no longer responding to anti-VEGF therapy, best-corrected visual acuity at least of 1.3 logMar. All patients were treated with Navilas guided by overlaid optical coherence tomography angiography (OCTA) images at the site of branching large neovascular trunks. RESULTS: Occlusion of large neovascular trunks successfully occurred in all nine included patients. OCTA analysis revealed, at 1 month follow up, MNV total area decreasing from 6.2 ± 3.1 to 2.6 ± 3.4 mm2. At 6 months follow up, mean MNV area was 3.3 ± 3.4 mm2 (p = 0.008). CONCLUSION: This preliminary study showed that Navilas treatment guided by OCTA may represent an attractive therapeutic option in advanced neovascular lesions secondary to AMD.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN THE DIAGNOSIS AND FOLLOW-UP OF RETINAL ARTERIAL MACROANEURYSMS.

PURPOSE: To describe optical coherence tomography angiography (OCTA) findings in retinal arterial macroaneurysm (RAM) associated with macular edema and to correlate OCTA findings with conventional multimodal imaging. METHODS: The clinical course, conventional multimodal imaging findings including fundus color photography, spectral domain optical coherence tomography (Spectralis; Heidelberg Engineering, Heidelberg, Germany), fluorescein angiography (Heidelberg Engineering), and OCTA (Optovue, Inc, Freemont, CA) findings at baseline and during the follow-up of two eyes (two patients) with symptomatic RAM associated with macular edema were documented. RESULTS: Two eyes of 2 patients, both women, aged 82 and 46 years, which presented with progressive visual decline, were included. On conventional multimodal imaging, exudative RAM with macular edema and lipid exudation were visible in both included eyes. On OCTA, the flow in the two RAM was detected at baseline. Case 1 was treated by focal laser photocoagulation. One month after treatment, fluorescein angiography showed RAM occlusion. Spectral domain optical coherence tomography showed a RAM and retinal thinning and a decreased central foveal thickness, resulting in visual acuity improvement. On OCTA, no flow was detectable in the RAM at 1-month follow-up. Case 2 was not treated at baseline. In this eye, no flow was detected on OCTA at 2-month follow-up. This suggests a spontaneous occlusion, which was confirmed by fluorescein angiography. CONCLUSION: Optical coherence tomography angiography is able to detect the presence or absence of flow signal within RAMs, which may both decrease the need for dye angiography in selected cases with exudative RAM and help in treatment decision making.

Deep Learning-Based Classification of Inherited Retinal Diseases Using Fundus Autofluorescence.

Background. In recent years, deep learning has been increasingly applied to a vast array of ophthalmological diseases. Inherited retinal diseases (IRD) are rare genetic conditions with a distinctive phenotype on fundus autofluorescence imaging (FAF). Our purpose was to automatically classify different IRDs by means of FAF images using a deep learning algorithm. Methods. In this study, FAF images of patients with retinitis pigmentosa (RP), Best disease (BD), Stargardt disease (STGD), as well as a healthy comparable group were used to train a multilayer deep convolutional neural network (CNN) to differentiate FAF images between each type of IRD and normal FAF. The CNN was trained and validated with 389 FAF images. Established augmentation techniques were used. An Adam optimizer was used for training. For subsequent testing, the built classifiers were then tested with 94 untrained FAF images. Results. For the inherited retinal disease classifiers, global accuracy was 0.95. The precision-recall area under the curve (PRC-AUC) averaged 0.988 for BD, 0.999 for RP, 0.996 for STGD, and 0.989 for healthy controls. Conclusions. This study describes the use of a deep learning-based algorithm to automatically detect and classify inherited retinal disease in FAF. Hereby, the created classifiers showed excellent results. With further developments, this model may be a diagnostic tool and may give relevant information for future therapeutic approaches.

Optical coherence tomography angiography findings of choroidal neovascularization secondary to laser injury: A case report.

PURPOSE: To report a case of choroidal neovascularization (CNV) secondary to laser injury imaged by optical coherence tomography angiography (OCTA) and treated by intravitreal anti-vascular endothelial growth factor (VEGF). OBSERVATIONS: A 14-year-old boy presented with vision loss and central scotoma in the right eye (RE) in the last month, after having stared at the beam of a laser pointer. At presentation, his best-corrected visual acuity (BCVA) in the RE was 20/40 and spectral-domain OCT (SD-OCT) showed an interruption of ellipsoid zone and the presence of an hyperrelfective lesion in subfoveal region. OCTA examination revealed the presence of a high-flow lesion on both outer retina to choriocapillaris (ORCC) and choriocapillaris segmentations. The patient was treated by one anti-VEGF injection: at one month follow-up his BCVA in the RE was 15/20. SD-OCT revealed the complete resolution of hyperreflective lesion and no detectable flow on OCTA. CONCLUSIONS AND IMPORTANCE: Retinal laser injury may be complicated by CNV. OCTA may non-invasively assess the presence of CNV, as well as treatment-response.

Comparison of pain experience and time required for pre-planned navigated peripheral laser versus conventional multispot laser in the treatment of diabetic retinopathy.

PURPOSE: To compare the pain and the duration of a panretinal photocoagulation (PRP) session using a conventional multispot laser (Quantel Medical) versus the Navilas® laser. METHODS: Treatment-naïve patients requiring bilateral PRP for diabetic retinopathy were included. For each patient, PRP was carried out using a conventional multispot laser (Quantel Medical, 577 nm) in one eye and the other eye was treated with the Navilas laser (OD-OS, 577 nm). For both PRP treatments, similar parameters (same power, exposure time, number, size and spacing of the spots) were used. For each eye, the duration of the session and the pain, measured using respectively a chronometer and a visual analogic scale (VAS), were recorded. RESULTS: Thirty-two eyes of sixteen patients (mean age 57 ± 13 SD, range 28-74), 11 men and 5 women, have been included. A mean of 1289 (1000-1500) spots with a mean power of 352 mW (300-450 mW) and an exposure time of 27 ms (20-30 ms) were delivered. The PRP session with the Navilas laser (mean time of 5.2 ± 0.8 min) was faster than with the conventional multispot laser (6.6 ± 1.1 min) (p = 0.02). Laser-induced pain was significantly reduced (VAS of 2.4 ± 1.6) using the Navilas laser compared to conventional laser (VAS: 7.1 ± 2) (p < 0.001). CONCLUSION: The PRP sessions using the Navilas laser were significantly faster and less painful than with a conventional multispot laser in our series.

Incidence of Macular Holes in the Fellow Eye without Vitreomacular Detachment at Baseline.

PURPOSE: To determine the rate of macular holes (MH) occurring in the fellow eyes of eyes with MH depending on the vitreomacular interface at baseline. METHODS: This was a retrospective study of patients operated on for idiopathic MH, with persistent vitreofoveal attachment in the fellow eye assessed by spectral-domain optical coherence tomography (SD-OCT). Follow-up lasted 6 months or more, and the main outcome was the occurrence of an MH. RESULTS: The 77 fellow eyes included had a mean follow-up of 34.11 ± 22.3 months (6-78.4). At baseline, 31 eyes had vitreomacular traction (VMT), 35 vitreomacular adhesion, and 11 no posterior vitreous detachment. MH occurred in 19.5% of the cases (15/77). The rate of MH was significantly higher among the eyes with VMT than among the eyes without VMT at baseline (35.5 vs. 8.7%; p = 0.009). CONCLUSION: One-third of eyes with VMT at baseline identified by SD-OCT will develop an MH in the following 5 years.

Optical Coherence Tomography Angiography to Distinguish Changes of Choroidal Neovascularization after Anti-VEGF Therapy: Monthly Loading Dose versus Pro Re Nata Regimen.

PURPOSE: To compare the qualitative and quantitative choroidal neovascularization (CNV) changes after antivascular endothelial growth factor (anti-VEGF) therapy in treatment-naïve and treated eyes with age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA). METHODS: Consecutive patients with neovascular AMD underwent multimodal imaging, including OCTA (AngioPlex, CIRRUS HD-OCT model 5000; Carl Zeiss Meditec, Inc., Dublin, OH) at baseline and at three monthly follow-up visits. Treatment-naive AMD patients undergoing anti-VEGF loading phase were included in group A, while treated patients were included in group B. Qualitative and quantitative OCTA analyses were performed on outer retina to choriocapillaris (ORCC) slab. CNV size was measured using a free image analysis software (ImageJ, open-source imaging processing software, 2.0.0). RESULTS: Twenty-five eyes of 25 patients were enrolled in our study (mean age 78.32 ± 6.8 years): 13 treatment-naïve eyes in group A and 12 treated eyes in group B. While qualitative analysis revealed no significant differences from baseline to follow-up in the two groups, quantitative analysis showed in group A a significant decrease in lesion area (P = 0.023); in group B, no significant change in the lesion area was observed during anti-VEGF therapy (P = 0.93). CONCLUSION: Treatment-naïve and treated eyes with CNV secondary to neovascular AMD respond differently to anti-VEGF therapy. This should be taken into account when using OCTA for CNV follow-up or planning therapeutic strategies.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY TO DISTINGUISH CHOROIDAL NEOVASCULARIZATION FROM MACULAR INFLAMMATORY LESIONS IN MULTIFOCAL CHOROIDITIS.

PURPOSE: To characterize the macular lesions in multifocal choroiditis using multimodal imaging (MMI) and to evaluate optical coherence tomography angiography (OCTA) in distinguishing neovascular from inflammatory lesions. METHODS: Retrospective review of medical records of consecutive patients diagnosed with multifocal choroiditis and macular involvement, between September 2014 and May 2016, were included. All patients underwent standard examination and MMI, including fundus color photography, fundus autofluorescence, fluorescein angiography, and spectral domain optical coherence tomography. They also underwent OCTA examination. Multimodal imaging and OCTA characteristics of inflammatory lesions and choroidal neovascularization (CNV) were compared. RESULTS: Eighteen eyes of 13 patients (11 females) were analyzed. The mean age was 42.9 ± 13.4 years. The lesions were first categorized as active or inactive CNV and active or inactive inflammatory lesions through conventional MMI. Using OCTA, an abnormal blood flow was observed in all active CNV (9/9) and most inactive CNV (5/6), but also in 2 of 14 lesions previously classified as active inflammatory lesions. On the contrary, no case of inactive inflammatory lesions showed abnormal blood flow. Therefore, the use of OCTA allowed a diagnosis of CNV that was not made through conventional MMI in 14% of cases of active inflammatory lesions. CONCLUSION: The combined findings of conventional imaging and OCTA demonstrate distinctive features of inflammatory lesions and CNV in multifocal choroiditis, allowing an appropriate management of these sight-threatening lesions. However, OCTA alone did not distinguish between active and inactive CNVs and should be integrated into an MMI approach.

The Evolution of the Plateau, an Optical Coherence Tomography Signature Seen in Geographic Atrophy.

Purpose: Histologic details of progression routes to geographic atrophy (GA) in AMD are becoming available through optical coherence tomography (OCT). We studied the origins and evolution of an OCT signature called plateau in eyes with GA and suggested a histologic correlate. Methods: Serial eye-tracked OCT scans and multimodal imaging were acquired from eight eyes of seven patients with GA and plateau signatures over a mean follow-up of 7.7 years (range, 3.7-11.6). The histology of unrelated donor eyes with AMD was reviewed. Results: Drusenoid pigment epithelial detachment (PED) on OCT imaging progressed into wide-based mound-like signatures with flattened apices characterized by a hyporeflective yet heterogeneous interior and an overlying hyperreflective exterior, similar to outer retinal corrugations previously ascribed to persistent basal laminar deposit (BLamD) but larger. These new signatures are described as "plateaus." An initial increase of the PED volume and hyporeflectivity of its contents was followed by a decrease in PED volume and thinning of an overlying hyperreflective band attributable to the loss of the overlying RPE leaving persistent BLamD. Both imaging and histology revealed persistent BLamD with defects through which gliotic Müller cell processes pass. Conclusions: Plateaus can be traced back to drusenoid PEDs on OCT imaging. We hypothesize that during progressive RPE atrophy, Müller cell extension through focal defects in the residual persistent BLamD may contribute to the heterogeneous internal reflectivity of these entities. The role of Müller cell activation and extension in the pathogenesis of AMD should be explored in future studies.

CHORIORETINAL WHITE DOT LESIONS IN EYES WITH MULTIFOCAL CHOROIDITIS AND TILTED DISK SYNDROME WITH INFERIOR STAPHYLOMA.

PURPOSE: To assess the influence of tilted disk syndrome (TDS) and inferior staphyloma on the macular clinical expression of MFC. METHODS: Medical charts of patients with MFC examined since 2009 were reviewed retrospectively. All patients underwent standard examination and multimodal imaging including fundus color photography, fundus autofluorescence, and spectral domain optical coherence tomography. Two groups of patients were compared : Group 1 with TDS and inferior staphyloma and Group 2 without. The number of MFC spots were counted and normalized to the surface area in a circle centered about the fovea. In Group 1, the number of lesions inside the staphyloma was compared with that outside the staphyloma. RESULTS: At baseline, 8 eyes in Group 1 had a mean (±SD) higher number of chorioretinal lesions outside the staphyloma (14.5 [±7.2]) than within the staphyloma (5 [±5.5]) (P = 0.017). All 11 eyes in Group 2 had chorioretinal lesions homogeneously distributed in the posterior pole. Eyes with TDS and inferior staphyloma developed choroidal neovascularization more frequently (6/8 eyes) than eyes without TDS (5/11 eyes) (P = 0.026). CONCLUSION: Inferior staphyloma associated with TDS could modulate the clinical expression of the inflammatory and neovascular process in eyes with MFC.

CYSTOID MACULAR EDEMA AND CYSTOID MACULAR DEGENERATION AS A RESULT OF MULTIPLE PATHOGENIC FACTORS IN THE SETTING OF CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To report the pathogenic factors that account for cystoid macular edema and cystoid macular degeneration in chronic central serous chorioretinopathy (CSC). METHODS: The clinical course and multimodal imaging findings, including fundus color photography, fundus autofluorescence, spectral-domain optical coherence tomography, and fluorescein angiography, of one eye with cystoid macular edema due to chronic CSC was documented. RESULTS: A 44-year old woman with a history of chronic CSC presented with progressive visual decline in the right eye. Best-corrected visual acuity was 20/40. Funduscopic examination revealed diffuse retinal pigment epithelial changes and macular edema. Fluorescein angiography demonstrated perifoveal microaneurysms and leakage in a petaloid configuration. Spectral-domain optical coherence tomography demonstrated cysts at the level of the inner nuclear layer, an epiretinal membrane, vitreomacular traction, and an attenuated retinal pigment epithelial band. Central subfield thickness was 486 µm. Three intravitreal injections of aflibercept were administered over 16 weeks following which there was resolution of leakage, release of vitreomacular traction, and resolution of microaneurysms. Central subfield thickness reduced to 379 µm, but persistent intraretinal cysts were observed. There was subjective improvement in visual symptoms, but Snellen acuity remained at 20/40. CONCLUSION: Intraretinal cystic changes in chronic CSC may be the result of multifactorial pathogenic factors and may represent the coexistence of cystoid macular edema and cystoid macular degeneration. Anti-vascular endothelial growth factor may play an important role in the treatment of cystoid macular edema caused by CSC.