Deep Learning for prediction of late recurrence of retinal detachment using preoperative and postoperative ultra-wide field imaging.

PURPOSE: To elaborate a deep learning (DL) model for automatic prediction of late recurrence (LR) of rhegmatogenous retinal detachment (RRD) using pseudocolor and fundus autofluorescence (AF) ultra-wide field (UWF) images obtained preoperatively and postoperatively. MATERIALS AND METHODS: We retrospectively included patients >18 years who underwent either scleral buckling (SB) or pars plana vitrectomy (PPV) for primary or recurrent RRD with a post-operative follow-up >2 years. Records of RRD recurrence between 6 weeks and 2 years after surgery served as a ground truth for the training of the deep learning (DL) models. Four separate DL models were trained to predict LR within the 2 postoperative years (binary outputs) using, respectively, UWF preoperative and postoperative pseudocolor images and UWF preoperative and postoperative AF images. RESULTS: A total of 412 eyes were included in the study (332 eyes treated with PPV and 80 eyes with SB). The mean follow-up was 4.0 ± 2.1 years. The DL models based on preoperative and postoperative pseudocolor UWF imaging predicted recurrence with 85.6% (sensitivity 86.7%, specificity 85.4%) and 90.2% accuracy (sensitivity 87.0%, specificity 90.8%) in PPV-treated eyes, and 87.0% (sensitivity 86.7%, specificity 87.0%) and 91.1% (sensitivity 88.2%, specificity 91.9%) in SB-treated eyes, respectively. The DL models using preoperative and postoperative AF-UWF imaging predicted recurrence with 87.6% (sensitivity 84.0% and specificity 88.3%) and 91.0% (sensitivity 88.9%, specificity 91.5%) accuracy in PPV eyes, and 86.5% (sensitivity 87.5%; specificity 86.2%) and 90.6% (sensitivity 90.0%, specificity 90.7%) in SB eyes, respectively. Among the risk factors detected with visualisation methods, potential novel ones were extensive laser retinopexy and asymmetric staphyloma. CONCLUSIONS: DL can accurately predict the LR of RRD based on UWF images (especially postoperative ones), which can help refine follow-up strategies. Saliency maps might provide further insight into the dynamics of RRD recurrence.

The impact of short-term postoperative face-up position on unintentional retinal displacement after pars plana vitrectomy for rhegmatogenous retinal detachment.

OBJECTIVE: To assess the effectiveness and safety of a rigorous short-term supine position in preventing inadvertent retinal displacement after pars plana vitrectomy (PPV) with gas tamponade for rhegmatogenous retinal detachment (RRD). METHODS: We conducted a retrospective observational analysis of a case series at two ophthalmological surgical centers. We included eyes diagnosed with macula-off RRD that maintained a strict face-up position for three hours immediately after PPV with intraoperative perfluorocarbon liquid (PFCL) and 20% sulfur hexafluoride (SF6) tamponade. Fundus autofluorescence (FAF) imaging was performed at one month post-operatively to identify unintentional retinal displacement through the detection of retinal vessel prints (RVPs) on FAF imaging using an ultrawide-field (UWF) imaging system. RESULTS: A total of 29 eyes with macula-off RRD were included in the study. The average age of the participants was 59.62 years. RRD involved one quadrant in two eyes, two quadrants in fourteen eyes, three quadrants in seven eyes, and four quadrants in six eyes. UWF-FAF imaging at one month follow-up after complete reattachment of the retina revealed RVPs in seven out of the 29 eyes (24.13%), with a mean displacement of 0.22 mm. In every case the displacement occurred downward. CONCLUSION: Our results suggest that adhering to a strict face-up position for three hours after PPV with PFCL and gas tamponade for macula-off RRD may lead to a low frequency and severity of inadvertent post-operative retinal displacement.

Hemorrhagic unilateral retinopathy: a report of multimodal imaging in three cases.

PURPOSE: To report three cases of hemorrhagic unilateral retinopathy, diagnosed by multimodal imaging. METHODS: Case report of 3 patients, 2 women and one man, aged 51, 74, and 52, respectively. RESULTS: Symptoms were acute floaters, blurred vision, or central scotoma, unilateral in all cases. The best-corrected visual acuity was 20/20 in the affected eye in 2 patients with a paracentral scotoma, and 20/160 in the third patient. Funduscopic examination revealed multiple unilateral posterior hemorrhages located in the Henle fiber layer in the macula and beneath the internal limiting membrane around the optic disc on spectral-domain optical coherence tomography (SD-OCT). Fluorescein angiography and indocyanine green angiography (ICGA) did not show any vascular abnormalities. SD-OCT angiography (SD-OCT-A) did not show any capillary drop-out or choroidal abnormalities. In all patients, the visual symptoms completely disappeared within a few weeks, with spontaneous regression of the hemorrhages. CONCLUSION: Hemorrhagic unilateral retinopathy is a rarely reported and poorly understood disorder. ICGA and SD-OCT-A did not allow better understanding the condition. No etiology has been associated with this entity so far. The spontaneous resolution of the present cases confirmed the favorable visual prognosis of the condition.

In vivo cone-photoreceptor density comparison between eyes with subretinal drusenoid deposits and healthy eyes using high magnification imaging.

PURPOSE: To compare photoreceptor density automated quantification in eyes with subretinal drusenoid deposits (SDD) and healthy controls using Heidelberg Spectralis High Magnification Module (HMM) imaging. METHODS: Twelve eyes of 6 patients with intermediate AMD, presenting with SDD were included, as well as twelve eyes of healthy controls. Individual dot SDD within the central 30° retina were examined with infrared confocal laser ophthalmoscopy, HMM, and spectral-domain optical coherence tomography (SD-OCT). Photoreceptor density analysis was performed on the best-quality image using the ImageJ Foci Picker plugin, after the removal of SDD from the HMM image. Correlations were made between the HMM quantified photoreceptor density, SD-OCT characteristics, stage, and number of SDD. RESULTS: Mean age was 75.17 ± 2.51 years in the SDD group (3 males, 3 females) versus 73.17 ± 3.15 years in the healthy control group (p = 0.2). Defects in the overlying ellipsoid zone were present on SD-OCT in 8/12 (66.66%) eyes. The mean ± standard deviation foci detected (i.e., cone photoreceptors) was 7123.75 ± 3683.32 foci/mm2 in the SDD group versus 13,253 ± 3331.00 foci/mm2 in the healthy control group (p = 0.0003). The number of SDD was associated with a reduction in foci density, p = 0.0055, r = - 0.7622. CONCLUSION: The decreased cone density in eyes with SDD may correlate with a decrease in retinal function in intermediate AMD eyes independent of neovascular complications or outer retinal pigment epithelial atrophy.

AUTOMATED DETECTION OF VITRITIS USING ULTRAWIDE-FIELD FUNDUS PHOTOGRAPHS AND DEEP LEARNING.

BACKGROUND/PURPOSE: Evaluate the performance of a deep learning algorithm for the automated detection and grading of vitritis on ultrawide-field imaging. METHODS: Cross-sectional noninterventional study. Ultrawide-field fundus retinophotographs of uveitis patients were used. Vitreous haze was defined according to the six steps of the Standardization of Uveitis Nomenclature classification. The deep learning framework TensorFlow and the DenseNet121 convolutional neural network were used to perform the classification task. The best fitted model was tested in a validation study. RESULTS: One thousand one hundred eighty-one images were included. The performance of the model for the detection of vitritis was good with a sensitivity of 91%, a specificity of 89%, an accuracy of 0.90, and an area under the receiver operating characteristics curve of 0.97. When used on an external set of images, the accuracy for the detection of vitritis was 0.78. The accuracy to classify vitritis in one of the six Standardization of Uveitis Nomenclature grades was limited (0.61) but improved to 0.75 when the grades were grouped into three categories. When accepting an error of one grade, the accuracy for the six-class classification increased to 0.90, suggesting the need for a larger sample to improve the model performances. CONCLUSION: A new deep learning model based on ultrawide-field fundus imaging that produces an efficient tool for the detection of vitritis was described. The performance of the model for the grading into three categories of increasing vitritis severity was acceptable. The performance for the six-class grading of vitritis was limited but can probably be improved with a larger set of images.

Multimodal imaging in early onset non-neovascular pigment epithelial detachments.

PURPOSE: To describe multimodal imaging of two cases of bilateral non-vascularized pigment epithelial detachments (PED) in young patients with a long-term follow-up. METHODS: A complete ophthalmological examination was performed at each follow-up visit including best corrected visual acuity (BCVA), intraocular pressure, slit lamp examination, spectral domain optical coherence tomography (SD-OCT), fluorescein and indocyanine green angiography, OCT angiography. RESULTS: Multimodal imaging of two women presenting avascular PED, aged 43 and 57, respectively, was described. In both patients, SD-OCT revealed a high central macular hyporeflective elevation corresponding with PED. Both patients showed a choroidal layer thicker than 420 µm. Fluorescein and indocyanine green angiography didn't show any choroidal neovascularization either at early or late frames. Cross-sectional and en face optical coherence tomography angiography (OCTA) didn't show any flow beneath the PED. During the follow up period one eye showed a retinal pigment epithelium tear and all eyes showed the presence of apical sub-retinal fluid and hyperreflective material on the top of the PED. None of the two patients showed any sign of atrophy during the follow-up period. CONCLUSION: The peculiar characteristics of the presented cases suggest that specific pathogenetic mechanisms, not necessarily related to age related macular degeneration, may play a key role in the development of these lesions. Whether early onset of such drusenoid PED is a specific entity resulting from a genetic deficit of lipid transporters in the RPE is unknown. Further genetic and metabolic studies should be conducted.

Phenomenology of spontaneous closure in degenerative and mixed type lamellar macular hole.

PURPOSE: To the describe OCT imaging characteristics of a cohort of patients showing spontaneously closing degenerative or mixed type lamellar macular holes (LMH) and to compare them to the ones of a sex and age matched group showing stable lesions. METHODS: Patients diagnosed with degenerative and mixed type LMHs showing OCT-documented spontaneous anatomical closure were retrospectively selected from 3 specialized retina centres. An equal number of age and sex matching subjects were randomly selected among patients with anatomically stable lesions. RESULTS: Eleven (11) spontaneously closing (SC group) and 11 stable (ST group) degenerative LMH with a mean follow up of 4 years were recruited. Hyperreflective inner border (HIB) and linear hyperreflectivity in the outer plexiform layer (LHOP) at baseline were significantly more prevalent in SC group in processed images (respectively p = 0.007 and p = 0.003). A borderline significance in lamellar hole associated epiretinal proliferation (LHEP) at last follow up was detected (p = 0.085). As for mixed type LMH, 10 patients for SC group and 10 for ST group were recruited. LHOP at baseline in processed images was significantly more prevalent in SC group (p = 0.005). CONCLUSIONS: Spontaneously closing LMHs show higher prevalence of HIB and LHOP at the beginning of the closing process, a difference which is enhanced by image processing. These signs might be a signal of microglial and Muller cells coordinated activation.

Refractive outcome in combined phacovitrectomy: Anterior segment changes and corrective factor for IOL power calculation improvement.

PURPOSE: To analyze differences in refractive outcome Δ (difference between postoperative and expected refractive error) and in anterior segment changes between cataract surgery patients and combined phacovitrectomy patients. We also aimed to provide a corrective formula allowing to minimise the refractive outcome Δ in combined surgery patients. METHODS: Candidates for phacoemulsification and combined phacovitrectomy (respectively PHACO and COMBINED groups) were prospectively enrolled in two specialised centres. Patients underwent best corrected visual acuity (BCVA) assessment, ultra-high speed anterior segment optical coherence tomography (OCT), gonioscopy, retinal OCT, slit lamp examination and biometry at baseline, 6 weeks postoperatively and 3 months postoperatively. RESULTS: No differences in refractive Δ, refractive error and anterior segment parameters were noted between PHACO and COMBINED group (109 and 110 patients respectively) at 6 weeks. At 3 months, COMBINED group showed a spherical equivalent of -0.29 ± 0.10 D versus -0.03 ± 0.15 D in PHACO group (p = 0.023). COMBINED group showed a significantly higher Crystalline Lens Rise (CLR), angle-to-angle (ATA) and anterior chamber width (ACW) and a significantly lower anterior chamber depth (ACD) and refractive Δ with all 4 considered formulas at 3 months. For IOL power lower than 15, a hyperopic shift was observed instead. CONCLUSIONS: Anterior segment OCT suggests anterior displacement of the effective lens position in patients undergoing phacovitrectomy. A corrective formula can be applied to IOL power calculation to minimize undesired refractive error.

Neuropathy, ataxia, retinitis pigmentosa: a case of a mother and two siblings.

AIM: We describe the ophthalmic manifestations of Neuropathy, ataxia, retinitis pigmentosa (NARP) syndrome in three related patients. METHODS: We examined a mother and her two children, who were carriers of the mt 8993T>G mutation. The mother, patient I, is the first known carrier within the family pedigree. Patients II and III are her children from a non-carrier father. NARP syndrome and the heteroplasmy levels were established prior to the first referral of the patients to the Ophthalmology department.We performed a visual acuity testing, followed by a biomicroscopic and fundus examination, as well as additional multimodal imaging testing: optical coherence tomography (OCT) and fundus autofluorescence (FAF), and functional testing: electroretinogram and visual field. RESULTS: All patients had the clinical manifestations of NARP syndrome, which were variably expressed symptomatically, on the fundus exams, electroretinogram, and visual fields. CONCLUSIONS: Once genetically established, NARP syndrome, as other mitochondrial disorders, has a very variable progression with different degrees of severity. A multimodal approach involving both neurological and ophthalmological diagnosis of NARP syndrome is necessary in order to establish the course of the disease and the measures to be taken.

An incipient late-onset retinal degeneration with a C1QTNF5 mutation: a case report with an 11-year follow-up.

PURPOSE: The purpose of this study was to describe and diagnose the difficulty in a long-term follow-up (eleven years) patient with a very early presentation of late-onset retinal degeneration (L-ORD) and the significance of electrophysiological examinations and follow-up in assessing undiagnosed inherited retinal diseases. METHODS: This is an observational case report of a 56-year-old woman, with scattered multiple yellow-white retinal dots firstly diagnosed as fundus albipunctatus. Ten years after presentation, a deterioration in rod and cone responses in ff-ERG was detected, which allowed us to discard the first diagnostic hypothesis and proceed with a genetic testing. RESULTS: Ten years after presentation, she presented a clear progression of the abnormal photoreceptor response with a cone and rod involvement in ff-ERG, which was not compatible with the previous suspicion of fundus albipunctatus. Six months later, genetic testing results together with the typical progression of atrophic patchy lesions in multimodal imaging allowed a certain diagnosis of L-ORD, caused by an already reported pathogenic variant in the C1QTNF5 gene (c.563C > T; p. Pro188 Leu). CONCLUSIONS: We demonstrate the importance of the ff-ERG examination and the follow-up (or ERG and imaging repetition) in the differential diagnosis of an incipient L-ORD, which can be easily misdiagnosed in the early stages, before the appearance of the characteristic chorioretinal atrophy seen with the progression of this rare disease.

The Impact of Diabetic Retinopathy on the Choriocapillaris in Neovascular AMD.

Purpose: To investigate the impact of diabetic retinopathy (DR) on morphological choriocapillaris (CC) modifications in eyes with type 1 macular neovascularization (MNV) secondary to AMD using optical coherence tomography angiography (OCTA). Methods: Eyes with AMD-related type 1 MNV with and without DR were prospectively included. We performed 3 × 3 mm OCTA scans at two visits: before the loading phase of intravitreal injections of aflibercept (T1) and 1 month after the last injection (T2). OCTA En face flow images of the CC were analyzed for flow deficit percentage (FD%), FD average area and FD number in a 500-µm-wide ring surrounding the dark halo (DH) around type 1 MNV. Results: A total of 65 eyes, out of which 30 eyes had mild DR, were included. In the group without diabetes, there was a gradual reduction in FD% in the CC ring around the DH after antiangiogenic therapy, indicating reperfusion of the CC (P = 0.003). However, in the DR group, there were no significant changes in CC parameters between the two study visits. Specifically, the FD% in the CC ring around the DH did not show a significant reduction at T2 compared with T1 values (P > 0.05). Furthermore, the comparison of the variation in FD% between the two groups was statistically significant. The nondiabetic group exhibited a gradual CC reperfusion after the loading phase of aflibercept, whereas the diabetic eyes did not show significant changes (P = 0.029). Conclusions: The CC surrounding the DH associated to type 1 MNV exhibited greater hypoperfusion in diabetic eyes compared with eyes without diabetes, both before starting therapy and after the loading phase. Hence, DR may be a potential risk factor in the development and progression of late-stage AMD and may also influence the response to antiangiogenic therapy.

Deep learning model for automatic differentiation of EMAP from AMD in macular atrophy.

To create a deep learning (DL) classifier pre-trained on fundus autofluorescence (FAF) images that can assist the clinician in distinguishing age-related geographic atrophy from extensive macular atrophy and pseudodrusen-like appearance (EMAP). Patients with complete outer retinal and retinal pigment epithelium atrophy secondary to either EMAP (EMAP Group) or to dry age related macular degeneration (AMD group) were retrospectively selected. Fovea-centered posterior pole (30° × 30°) and 55° × 55° degree-field-of-view FAF images of sufficiently high quality were collected and used to train two different deep learning (DL) classifiers based on ResNet-101 design. Testing was performed on a set of images coming from a different center. A total of 300 patients were recruited, 135 belonging to EMAP group and 165 belonging to AMD group. The 30° × 30° FAF based DL classifier showed a sensitivity of 84.6% and a specificity of 85.3% for the diagnosis of EMAP. The 55° × 55° FAF based DL classifier showed a sensitivity of 90% and a specificity of 84.6%, a performance that was significantly higher than that of the 30° × 30° classifer (p = 0.037). Artificial intelligence can accurately distinguish between atrophy caused by AMD or by EMAP on FAF images. Its performance are improved using wide field acquisitions.

Optical coherence tomography angiography analysis of changes in the retina and the choroid after hemodialysis for end stage kidney disease.

PURPOSE: To study effects of hemodialysis (HD) on retinal and choroidal vasculature in patients with end-stage kidney disease (ESKD) using optical coherence tomography angiography (OCTA). METHODS: In this prospective study, we investigated eyes of patients undergoing hemodialysis for ESKD from Mondor University Hospital. Only one eye/patient was considered. Subfoveal choroidal thickness (SCT) was measured on enhanced-depth imaging optical coherence tomography (EDI-OCT) before and after the hemodialysis session. OCTA was used to extract retinal vascular density (superficial and deep capillary plexus, SCP, DCP) and choriocapillaris non-perfusion. Clinical, demographic and biological parameters (Blood B-Nitric Peptid rate prior to HD session) were reviewed. RESULTS: Twenty patients (mean age 53.2 ± 13.6 years, 10 males and 10 females) were included in this prospective study. SCT significantly decreased after the HD session (234.3 ± 56.14 µm before HD to 211.9 ± 60.79 µm after hemodialysis (Wilcoxon signed-rank test, p = 0.003)). Non-perfusion in the choriocapillaris significantly increased after HD (41.65 ± 3.58 before HD, 42.95 ± 3.19 after HD, p = 0.036) while no significant modification of the vascular density was observed in the retinal vasculature (SCP, DCP) around the macular zone or the optic nerve. An increased plasma B-Nitric Peptide (BNP) level prior to the onset of the HD session was significantly correlated with the decrease of the SCT (r = 0.45, p = 0.043). CONCLUSION: Hemodialysis in patients with ESKD is associated with a significant decrease in SCT and an increase in non-perfusion in the choriocapillaris on OCTA. A High BNP level prior to the onset of the hemodialysis appears to be correlated with the decrease in SCT.

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.

Correlation between AI-measured lacquer cracks extension and development of myopic choroidal neovascularization.

OBJECTIVES: To investigate the correlation between the AI-measured area of the lacquer cracks (LC) at their first detection and the occurrence of a choroidal neovascularization (CNV) during the follow-up in patients affected by pathologic myopia. Secondary outcome was the detection of a correlation between the time to onset of CNV with both baseline LC area and LC area increase during follow-up. METHODS: Optical coherence tomography (OCT) acquisitions of patients diagnosed with LC were retrospectively analysed. The study population was divided in a CNV group (showing the documented onset of a CNV) and a n-CNV group (no CNV development during follow-up). LC area was measured using MatLab software after the application of a customized method for LC segmentation on infrared (IR) enface images. RESULTS: Forty-five (45) patients with a mean follow-up of 4.9 ± 1.5 years were included. LC area at baseline was 2.82 ± 0.54 mm2 and 1.70 ± 0.49 mm2 in CNV (20 patients) and n-CNV group (25 patients) group respectively (p < 0.001). LC area increase was significantly higher in CNV group (p < 0.001). Time to onset of CNV was linearly correlated with both LC area at baseline (p = 0.006) and LC area increase (p < 0.001). CONCLUSIONS: Myopic CNV development is associated with lager LC areas and higher LC area increase during time. Earlier CNV onset is inversely correlated with LC area and LC area increase.