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Purpose: To evaluate the safety of subretinal injection of cord blood platelet-rich plasma (CB-PRP) and its possible effect in eyes affected by geographic atrophy (GA) associated with dry age-related macular degeneration (d-AMD). Design: Interventional, open-label study started in January 2021 with follow-up at 12 months (the Si.Cord Study). This study was a single-center, nonrandomized, sequential-assigned clinical trial conducted in Rome, Italy, at Fondazione Policlinico Universitario Agostino Gemelli IRCCS (ClinicalTrials.gov NCT04636853). Participants: Thirteen patients (26 eyes) with bilateral d-AMD-related GA were enrolled. One eye from each patient (with more advanced GA) underwent CB-PRP treatment, and the fellow eye was considered the control. All patients participated in follow-up at 12 months. Intervention: All 13 eyes received 23-gauge (G) vitrectomy and subretinal injection of CB-PRP using a 41-gauge needle. Main Outcomes and Measures: Best-corrected visual acuity (BCVA) with ETDRS letters, central macular thickness using OCT, and atrophic area measured on en face OCT images were assessed at baseline, 1, 3, 6, and 12 months. Results: The BCVA in the treated group was 34.46 ± 20.8 ETDRS at baseline, 40.84 ± 20.52 at 1 month, 40.07 ± 20.34 at 3 months, 39.38 ± 19.84 at 6 months, and 35.84 ± 18.38 at 12 months. In the untreated group, the BCVA was 53 ± 21.1 ETDRS letters at baseline, 51.54 ± 20.99 at 1 month, 46.62 ± 19.47 at 3 months, 46.85 ± 18.58 at 6 months, and 43.92 ± 17.97 at 12 months (2-way analysis of variance: interaction of treatment by eye or time, P = 0.084). Central macular thickness did not show a significant intereye difference at 12 months (P = 0.97). The atrophic geographic areas tended to increase in both treated and fellow eyes at 12 months (P < 0.0001). No inflammatory reaction, endophthalmitis, retinal detachment, uveitis, or other complications due to the subretinal injection of CB-PRP were observed during the follow-up. Conclusions: Subretinal injection of CB-PRP could be safely used for d-AMD in its GA form. Despite its safety, a larger cohort of patients, and probably a new way of administration, will be needed to understand whether the CB-PRP could have a role in the GA treatment. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Abstract Age related macular degeneration (AMD) represents a leading cause of vision loss and it is expected to affect 288 million people by 2040. During the last decade, machine learning technologies have shown great potential to revolutionize clinical management of AMD and support research for a better understanding of the disease. The aim of this review is to provide a panoramic description of all the applications of AI to AMD management and screening that have been analyzed in recent past literature. Deep learning (DL) can be effectively used to diagnose AMD, to predict short term risk of exudation and need for injections within the next 2 years. Moreover, DL technology has the potential to customize anti-VEGF treatment choice with a higher accuracy than expert human experts. In addition, accurate prediction of VA response to treatment can be provided to the patients with the use of ML models, which could considerably increase patients’ compliance to treatment in favorable cases. Lastly, AI, especially in the form of DL, can effectively predict conversion to GA in 12 months and also suggest new biomarkers of conversion with an innovative reverse engineering approach.

Abstract Optical coherence tomography angiography (OCTA) has extensively enhanced our comprehension of eye microcirculation and of its associated diseases. In this narrative review, we explored the key concepts behind OCTA, as well as the most recent evidence in the pathophysiology of age-related macular degeneration (AMD) made possible by OCTA. These recommendations were updated since the publication in 2020, and are targeted for 2023. Importantly, as a future perspective in OCTA technology, we will discuss how artificial intelligence has been applied to OCTA, with a particular emphasis on its application to AMD study.

Abstract 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.

Purpose: Corneal perforation due to severe melting is a very dangerous, sight-threatening condition requiring immediate management due to the high risk of endophthalmitis and critical hypotony. In the case of perforated corneal grafts, retransplantation is usually postponed to avoid the detrimental effects of inflammation on the new graft. We describe the first case of the use of a TutoPatch graft for emergency replacement of a lamellar graft perforation over acute infectious total melting. Observations: A 42-year-old male patient presented to the Emergency Department with pain in the left eye, which was red photophobic. He had been treated with bilateral deep anterior lamellar keratoplasty (DALK) for advanced keratoconus 5 years previously and had been experiencing recurrent corneal ulcers in the left eye within the last 8 months. Clinical examination documented corneal perforation over acute infectious melting involving the total graft surface in the left eye. The infected graft was removed along with the perforated infected residual Descemet membrane, and a double-layer TutoPatch covering was sutured to the host's margin with 10.0 nylon. The covering was left in place for three weeks, allowing the patient to undergo retransplant three weeks later without complications. Conclusions and importance: TutoPatch covering can be safely used as an easy-to-preserve emergency material for a temporary bridge to retransplantation in large acute infectious corneal melting.

Purpose: Geometric perfusion deficit (GPD) is a newly described OCT angiography (OCTA) parameter identifying the total area of presumed retinal ischemia. The aim of our study is to characterize differences in GPD and other common quantitative OCTA parameters between macular full field, perivenular zones, and periarteriolar zones for each clinical stage of nonproliferative diabetic retinopathy (DR) and to assess the influence of ultrahigh-speed acquisition and averaging on the described differences. Design: Prospective observational study. Participants: Forty-nine patients, including 11 (22.4%) with no sign of DR, 12 (24.5%) with mild DR, 13 (26.5%) with moderate DR, and 13 (26.5%) with severe DR. Patients with diabetic macular edema, proliferative DR, media opacity, head tremor, and overlapping retinal diseases or systemic diseases influencing OCTA were excluded. Methods: OCT angiography was performed 3 times for each patient: 1 using Solix Fullrange single volume (V1) mode, 1 using Solix Fullrange 4 volumes mode with automatically averaged scan (V4), and 1 using AngioVue. Main Outcome Measures: Full macular, periarteriolar, and perivenular perfusion density (PD), vessel length density (VLD), vessel density index, and GPD for both the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Results: In patients showing no sign of DR, PD and VLD were significantly lower in the perivenular area in both the DCP and SCP using V1 and V4, whereas GPD was significantly higher in the perivenular zone in the DCP and SCP with all 3 devices. In patients with mild DR, all 3 measurements (PD, VLD, and GPD) were significantly different in the perivenular zone with all 3 devices. In patients with moderate DR, PD and VLD were lower in the DCP and SCP when measured with V1 and V4. Moreover, GPD was higher in the perivenular zone in the DCP with all 3 devices, whereas only V4 detected a difference in the SCP. In severe DR, only V4 detected a lower PD and VLD and a higher GPD in the DCP of the perivenular zone. V4 also detected a higher GPD in the SCP. Conclusions: Geometric perfusion deficit highlights prevalent perivenular location of macular capillary ischemia in all stages of DR. In severe DR patients, only averaging technology allows detection of the same finding. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Abstract Initial stages of Best vitelliform macular dystrophy (BVMD) and adult vitelliform macular dystrophy (AVMD) harbor similar blue autofluorescence (BAF) and optical coherence tomography (OCT) features. Nevertheless, BVMD is characterized by a worse final stage visual acuity (VA) and an earlier onset of critical VA loss. Currently, differential diagnosis requires an invasive and time-consuming process including genetic testing, electrooculography (EOG), full field electroretinogram (ERG), and visual field testing. The aim of our study was to automatically classify OCT and BAF images from stage II BVMD and AVMD eyes using a deep learning algorithm and to identify an image processing method to facilitate human-based clinical diagnosis based on non-invasive tests like BAF and OCT without the use of machine-learning technology. After the application of a customized image processing method, OCT images were characterized by a dark appearance of the vitelliform deposit in the case of BVMD and a lighter inhomogeneous appearance in the case of AVMD. By contrast, a customized method for processing of BAF images revealed that BVMD and AVMD were characterized respectively by the presence or absence of a hypo-autofluorescent region of retina encircling the central hyperautofluorescent foveal lesion. The human-based evaluation of both BAF and OCT images showed significantly higher correspondence to ground truth reference when performed on processed images. The deep learning classifiers based on BAF and OCT images showed around 90% accuracy of classification with both processed and unprocessed images, which was significantly higher than human performance on both processed and unprocessed images. The ability to differentiate between the two entities without recurring to invasive and expensive tests may offer a valuable clinical tool in the management of the two diseases.

To describe a surgical variant for non-valved glaucoma drainage device implants using an easily removable non-absorbable double suture into the lumen of the tube. A retrospective, non-comparative case series of 10 patients who underwent a non-valved glaucoma drainage device implant with an endoluminal double-suture for refractory glaucoma. The sutures were easily removed postoperatively without the need for an operating room. Intraocular pressure, number of medications, and early and late complications were evaluated with a follow-up of 12 months. None of the eyes that underwent an operation developed early or late complications. The first endoluminal suture was removed in all eyes with a mean time of removal of 30 ± 7 days. The second suture was removed in all eyes with a mean time of removal of 90 ± 7 days. No complications were noted, either, after or during suture removal. The mean preoperative IOP was 27.3 ± 4.0 and the postoperative IOP, at the end of the follow-up, was 12.7 ± 1.4. At the end of the follow-up, six patients (60%) achieved complete success and four patients (40%) achieved qualified success. In conclusion, in our case series, the surgical variant allowed for a safe and gradual regulation of the flow during postoperative management. Considering the efficacy of non-valved glaucoma drainage devices, an improvement in the safety profile allows surgeons to broaden the surgical indications.

Macular neovascularization (MNV) and geographic atrophy can complicate age-related macular degeneration (AMD) and lead to severe visual acuity reduction. Despite the medical treatments available, with a defect in the retinal pigmented epithelium (RPE) there is no possibility of restoring acceptable visual acuity. We evaluated postoperative outcomes in patients affected by advanced AMD who underwent subretinal implant of the human amniotic membrane (hAM) as a source of pluripotent stem cells. This retrospective, consecutive, non-randomized interventional study included 23 eyes of 21 patients affected by AMD complicated by MNV, and five eyes of five patients affected by geographic atrophy. All eyes underwent a pars plana vitrectomy, neovascular membrane removal for the MNV group, a subretinal implant of hAM, and gas tamponade, and were followed for 12 months. The primary study outcome was visual acuity improvement. Secondary outcomes were postoperative complications, OCT-angiography parameters correlated with best-corrected visual acuity (BCVA) and MNV recurrence. The mean preoperative BCVA was 1.9 logMAR, and the mean final BCVA value was 1.2 logMAR. In the MNV group, the mean BCVA improved from 1.84 logMAR to 1.26 logMAR, and from 1.84 logMAR to 1.32 logMAR in the geographic atrophy group. No MNV recurrence was evident in 12 months of follow-up. An OCT-angiography scan was used to evaluate the retinal vascularization in the treated eye, which showed a high correlation between BCVA and deep vascular density. This study demonstrates the hAM potential and safety in promoting a partial restoration of retinal function together with an increase in visual acuity.

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.

Background: Endothelial cells damage and thromboinflammation are considered key elements in the generation of organ impairment in patients with COVID-19 disease. The endothelial function is evaluated by measuring flow-mediated dilation (FMD). We aimed to analyze the association between FMD impairment and retinal vascular parameters in early post-COVID-19 patients. 00118-00199Tomography (OCT), OCT Angiography (OCTA) and slit lamp examination were performed. FMD ≤ 7% was considered as pathological. Our primary outcome was to assess potential differences in the radial peripapillary capillary plexus flow index (RPCP-FI) and RPCP density (RPCP-D) values between post-COVID-19 patients with and without FMD impairment. The associations of other retinal vascular parameters with FMD impairment were assessed as secondary endpoints. Results: FMD impairment was detected in 31 patients (37.8%). RPCP-FI (p = 0.047), age (p = 0.048) and prevalence of diabetes (p = 0.046) significantly differed in patients with FMD ≤ 7% in regression analysis. RPCP-FI was linearly correlated with FMD values (R = 0.244, p =0.027). SCT was found to be lower in patients with impaired FMD (p = 0.004), although this difference was only a trend in binary logistic regression output (p = 0.07). Conclusions: Early post-COVID-19 patients showed a higher prevalence of FMD impairment compared to the general population. Age, diabetes and RPCP-FI were independently correlated with the presence of endothelial impairment in the early post-infective period.

Lamellar macular holes (LMHs) may show morphological and functional deterioration over time, yet no definite prognostic factor for progression has been identified. Since neurovascular retinal unit impairment may take part in neurodegeneration, we compare progressive LMHs to stable ones in optical coherence tomography (OCT) angiography parameters. Methods: OCT B scans of eyes with LMH were analyzed to detect the presence of tissue loss (TL) over time, allowing us to identify a TL group and a stable (ST) group (14 patients each). The best corrected visual acuity (BCVA) at each considered imaging time point was collected. Lastly, patients underwent macular OCT angiography. Results: BCVA at last follow up was significantly reduced in the TL group compared to both the ST group and TL group baseline assessment. SCP foveal vessel density (VD), SCP and deep capillary plexus (DCP) perfusion density (PD) and parafoveal PD were lower in the TL group. Linear correlations between quantitative TL over time and parafoveal PD in SCP and between the speed of TL and BCVA variation during follow up were also detected. Conclusions: TL in LMHs is associated with both OCT angiography modifications and BCVA deterioration over time. We suggest these findings to be a manifestation of foveal Muller cell impairment in progressive LMHs.

There is no consensus on whether amblyopia affects the retinal vascular plexus and morphology. Previous studies focused on the differences between amblyopic patients and normal controls without evaluating amblyopic eyes after patching. To evaluate differences in the superficial vascular density of amblyopic eyes, normal eyes, and amblyopic eyes reaching normal BCVA after patch therapy, OCTA was used. All patients underwent a comprehensive ophthalmological examination, including visual acuity, refraction, ocular motility tests, and anterior and posterior segment examination. OCTA was performed by an expert physician using the Zeiss Cirrus 5000-HD-OCT Angioplex (Carl Zeiss, Meditec, Inc., Dublin, OH, USA). OCTA scans were performed using a 3 × 3 mm2 and 6 × 6 mm2 fovea-centered image setting. The mean outer macular vessel density in the previously amblyopic group was 19.15 ± 0.51%. This was statistically significantly higher than in both the amblyopic group (18.70 ± 1.14%) and the normal controls (18.18 ± 1.40%) (p = 0.014). The previously amblyopic group also significantly differed from both normal controls and amblyopic eyes with regards to the inner (p = 0.011), outer (p = 0.006), and full (p = 0.003) macular perfusion. Finally, linear regression analysis revealed that BCVA was linearly correlated to outer perfusion in amblyopic (p = 0.003) and ex amblyopic eyes (p < 0.001). Considering the cross-sectional nature of our study, from our results, we can only hypothesize a possible correlation between light stimulation and retinal vasculature development. However, further longitudinal studies are needed to support this hypothesis.