Swept-source optical coherence tomography angiography findings in a case of primary vitreoretinal lymphoma over a three-year follow-up.

BACKGROUND: Vitreoretinal lymphoma (VRL) still represents a diagnostic challenge for retinal specialists. Early diagnosis and treatment are critical for a better prognosis. Several diagnostic tools have proven helpful in the identification of VRL abnormalities. However, swept-source OCT angiography (SS-OCT-A) findings and their long-term follow-up are yet to be explored. CASE PRESENTATION: a 42-year-old man presented with blurred vision in his left eye for 2 weeks. He denied any systemic symptoms. A multimodal imaging examination was performed, raising the clinical suspicion of VRL and guiding the ensuing diagnostic procedures. The patient underwent treatment and at the last FU visit three years later, no disease signs were present on fundus examination, nor on oncologic evaluation. Some novel SS-OCT-A features were identified, and uncommonly reported findings were examined over a long-term follow-up. At baseline multiple hyperreflective alterations were detected on the enface outer retina slabs and choriocapillary analysis revealed low reflectance areas in the foveal and parafoveal areas. One month after the first presentation, multiple hyperreflective retinal lesions in a vertical shape were detected on OCT which appeared on midretinal slabs of enface SS-OCT-A as hyperreflective spots mainly located near second-order retinal vessels. These alterations remarkably reduced after treatment. CONCLUSION: SS-OCT-A may be a useful imaging technique in the detection of VRL, providing ophthalmologists additional findings that assist the diagnosis and follow-up of this disease. This may prove useful for a more timely and precise diagnosis, prompt therapy, and treatment response monitoring. The original aspects found in this case may provide grounds for future studies, ultimately fostering a better understanding of the disease.

Fovea-sparing internal limiting membrane peeling with inverted flap technique versus standard internal limiting membrane peeling for symptomatic myopic foveoschisis.

To study the long-term outcomes of standard ILM peeling and fovea sparing with inverted flap (FSIF) peeling for symptomatic myopic foveoschisis (MF). This retrospective observational study included 36 eyes of 34 consecutive patients who underwent vitrectomy with standard ILM peeling and FSIF peeling for MF between April 2012 and march 2020. The primary outcome measures included best-corrected visual acuity (BCVA) and central foveal thickness (CFT) at 1 month and final visit and postoperative development of macular hole. There were 14 eyes in the standard ILM peeling group and 22 eyes and in the FSIF peeling groups with a mean FU of 34.2 months (SD 23.3; min. 12-max. 96) and 27.7 months (SD 14.9; min. 12-max. 63), respectively. In both groups BCVA was not significantly improved at 1 month but improved at last visit from 0.55 ± 0.21 to 0.37 ± 0.29 in the standard ILM peeling group (P = 0.0154) and from 0.57 ± 0.27 to 0.28 ± 0.23 in the FSIF peeling group (P < 0.0001). At 1 month and final visit CMT decreased from 572 ± 183.5 µm to 277.5 ± 95.2 µm and to 250.4 ± 96.1 µm, respectively, in the standard ILM peeling group and from 589.9 ± 189.8 µm to 383 ± 110.1 µm and 162.3 ± 74.8 µm in the FSIF peeling group (P < 0.001 for both groups at both time-points). The preoperative and postoperative BCVA and CMT showed no significant differences between groups. Three of the eyes in the standard ILM peeling group developed postoperative macular hole at 1, 10, 24 months, respectively, and none of the eyes in the FSIF peeling group. Multivariate analysis revealed that a better BCVA was the only independent factor correlated with the final BCVA. In this study, standard ILM peeling and FSIF peeling were both beneficial in improving the anatomy and function of eyes with MF. Postoperative MH may occur up to 2 years after standard peeling and seem effectively prevented by FSIF peeling.

Towards a Long-Read Sequencing Approach for the Molecular Diagnosis of RPGRORF15 Genetic Variants.

Sequencing of the low-complexity ORF15 exon of RPGR, a gene correlated with retinitis pigmentosa and cone dystrophy, is difficult to achieve with NGS and Sanger sequencing. False results could lead to the inaccurate annotation of genetic variants in dbSNP and ClinVar databases, tools on which HGMD and Ensembl rely, finally resulting in incorrect genetic variants interpretation. This paper aims to propose PacBio sequencing as a feasible method to correctly detect genetic variants in low-complexity regions, such as the ORF15 exon of RPGR, and interpret their pathogenicity by structural studies. Biological samples from 75 patients affected by retinitis pigmentosa or cone dystrophy were analyzed with NGS and repeated with PacBio. The results showed that NGS has a low coverage of the ORF15 region, while PacBio was able to sequence the region of interest and detect eight genetic variants, of which four are likely pathogenic. Furthermore, molecular modeling and dynamics of the RPGR Glu-Gly repeats binding to TTLL5 allowed for the structural evaluation of the variants, providing a way to predict their pathogenicity. Therefore, we propose PacBio sequencing as a standard procedure in diagnostic research for sequencing low-complexity regions such as RPGRORF15, aiding in the correct annotation of genetic variants in online databases.

The light-dependent pseudo-capacitive charging of conjugated polymer nanoparticles coupled with the depolarization of the neuronal membrane.

The mechanism underlying visual restoration in blind animal models of retinitis pigmentosa using a liquid retina prosthesis based on semiconductive polymeric nanoparticles is still being debated. Through the application of mathematical models and specific experiments, we developed a coherent understanding of abiotic/biotic coupling, capturing the essential mechanism of photostimulation responsible for nanoparticle-induced retina activation. Our modeling is based on the solution of drift-diffusion and Poisson-Nernst-Planck models in the multi-physics neuron-cleft-nanoparticle-extracellular space domain, accounting for the electro-chemical motion of all the relevant species following photoexcitation. Modeling was coupled with electron microscopy to estimate the size of the neuron-nanoparticle cleft and electrophysiology on retina explants acutely or chronically injected with nanoparticles. Overall, we present a consistent picture of electrostatic depolarization of the bipolar cell driven by the pseudo-capacitive charging of the nanoparticle. We demonstrate that the highly resistive cleft composition, due to filling by adhesion/extracellular matrix proteins, is a crucial ingredient for establishing functional electrostatic coupling. Additionally, we show that the photo-chemical generation of reactive oxygen species (ROS) becomes relevant only at very high light intensities, far exceeding the physiological ones, in agreement with the lack of phototoxicity shown in vivo.

Use of Heavy Silicon Oil as Intraocular Tamponade for Inferior Retinal Detachment Complicated by Proliferative Vitreoretinopathy: A Multicentric Experience.

INTRODUCTION: This is a multicentric study on the use of heavy silicon oil (HSO) as an intraocular tamponade for inferior retinal detachment (RD) complicated by proliferative vitreoretinopathy (PVR). METHODS: 139 eyes treated for RD with PVR were included in the study. 10 (7.2%) were affected by primary RD with inferior PVR, while 129 (92.8%) were affected by recurrent RD with inferior PVR. 102 eyes (73.9%) had received a silicon oil (SO) tamponade in a previous intervention prior to receiving HSO. Mean follow-up was 36.5 (standard deviation = 32.3) months. RESULTS: The median interval between HSO injection and removal was 4 months (interquartile range: 3). At the time of HSO removal, the retina was attached in 120 eyes (87.6%), whereas in 17 eyes (12.4%), it had re-detached while the HSO was in situ. 32 eyes (23.2%) showed recurrent RD. A subsequent RD relapse was observed in 14.2% of cases with no RD at the time of HSO removal, and in 88.2% if an RD was present at the time of HSO removal. Advancing age showed a positive association with retinal attachment at the end of follow-up, while the risk of RD relapse at the end of the follow-up showed a significant negative association with HSO tamponade duration and with the use of SO rather than air or gas as post-HSO tamponade materials. Mean best corrected visual acuity was 1.1 logarithm of minimum angle of resolution at all follow-up time points. 56 cases (40.3%) needed treatment for elevated intraocular pressure (IOP), with which no clinically relevant variables were associated during follow-up. CONCLUSION: HSO represents a safe and effective tamponade in cases of inferior RD with PVR. The presence of RD at the time of HSO removal is a negative prognostic factor for the development of a subsequent RD relapse. According to our findings, in cases of RD at the time of HSO removal, a short-term tamponade should definitely be avoided, in favor of SO. Special attention must be paid to the risk of IOP elevation, and patients should be closely monitored.

Lamellar macular defects: are degenerative lamellar macular holes truly degenerative?

Purpose: To investigate morpho-functional changes after surgical treatment for ERM foveoschisis or lamellar macular hole (LMH), and to evaluate whether the two entities are associated with different healing processes and long-term outcomes. Design: Retrospective interventional case series. Methods: A total of 56 eyes, treated for lamellar macular defects and followed up for 24 months, were enrolled. The eyes were divided into two groups: 34 with ERM foveoschisis and 22 with LMH. Changes in the following features were evaluated and compared between the two groups: best-corrected visual acuity (BCVA), external limiting membrane (ELM) and ellipsoid zone (EZ) defects, central foveal thickness (CFT), and autofluorescence (FAF) diameter and area. Results: After surgery, progressive BCVA improvement was observed with no significant difference between the two groups (p-value: 0.06). An increased number of eyes with intact outer-retinal layers was found both in the ERM foveoschisis and LMH groups. FAF diameter and area decreased significantly throughout the FU with no significant difference between the two groups (p-value: 0.2). Conclusion: In the present study, significant functional and microstructural improvements were observed after surgery for both ERM foveoschisis and LMH, demonstrating considerable repair potential in both types of lamellar defects. These findings question the true "degenerative" nature of LMH.

Infrared analysis in the aqueous humor of patients with uveitis: Preliminary results.

Inflammatory processes affecting the uvea result in a temporary o permanent blurred vision and represent an important cause of visual impairment worldwide. It is often hard to make a precise diagnosis which is dependent on the clinical expertise, diagnostic tests, laboratory investigations in blood and sometimes in the aqueous humor (AH). With the aim of obtaining proof of principle Fourier Transformed Infrared (FT-IR) absorbance spectroscopy was applied to study the molecular composition of 72 AH samples collected in 26 patients with uveitis and in 44 controls. The unsupervised exploration of the internal structure of the dataset by principal component analysis reduced hundreds IR variables to those most representative allowing to obtain the predictive model that distinguished the AH spectra of patients with uveitis from controls. The same result was obtained by unsupervised agglomerative cluster analysis. After labeling the spectra with some clinical information it was observed that most severe uveitis with active processes were grouped separately from chronic and relapsing uveitis and controls. The consistence of prediction models is discussed in the light of supporting etiological diagnosis by machine learning processes. In conclusion, proof of principle has been obtained that the IR spectral pattern of AH may reflect particular uveal diseases.

The p-ERG spatial acuity in the biomedical pig under physiological conditions.

Pigs are becoming an important pre-clinical animal species for translational ophthalmology, due to similarities with humans in anatomical and physiological patterns. Different models of eye disorders have been proposed, and they are good candidates to assess biocompatibility/functionality of retinal prostheses. Electroretinography is a common tool allowing to gain information on retinal function, with several types of electroretinogram (ERG) been implemented including full field (ff-ERG), multifocal (mf-ERG) and pattern (p-ERG). p-ERG represents a valuable tool to monitor Retinal Ganglion Cells (RGCs) activity and can be used to calculate p-ERG spatial acuity. Unfortunately, scarce methodological data are available regarding recording/interpretation of p-ERG and retinal acuity in biomedical pigs yet enhancing knowledge regarding pig vision physiology will allow for more refined and responsible use of such species. Aim of this study was to record p-ERG in juvenile pigs to functionally assess visual acuity. Six female hybrid pigs underwent two p-ERG recording sessions at 16 and 19 weeks of age. Photopic ff-ERG were also recorded; optical coherence tomography (OCT) and histology were used to confirm retinal integrity. ff-ERG signals were repeatable within/across sessions. All p-ERG traces consistently displayed characterizing peaks, and the progressive decrease of amplitude in response to the increment of spatial frequency revealed the reliability of the method. Mean p-ERG spatial acuities were 5.7 ± 0.14 (16 weeks) and 6.2 ± 0.15 cpd (19 weeks). Overall, the p-ERG recordings described in the present work seem reliable and repeatable, and may represent an important tool when it comes to vision assessment in pigs.

Destructive inflammatory reaction after an autologous retinal pigment epithelium and choroid transplantation: no detection of an auto-immune response.

PURPOSE: Five patients who underwent uncomplicated retinal pigment epithelium (RPE)-choroid transplantation for neovascular age-related macular degeneration developed a destructive inflammatory reaction causing subretinal fluid accumulation and extensive RPE atrophy in the graft. We hypothesized that this inflammation could be caused by an auto-immune response against the graft, resulting in circulating auto-antibodies. The aim of our study was to examine a potential autoimmune origin, which would allow a more targeted therapy approach. METHODS: Five above-mentioned patients and four control groups of five patients each were included: 1) after uncomplicated RPE-choroid transplantation, 2) after full macular translocation, 3) treated with anti-vascular endothelial growth factor, and 4) healthy controls. Histopathology of rejected graft tissue was performed using standard procedures. Presence of RPE-choroid autoantibodies in serum was examined by indirect immunofluorescence and Western blot, and human leukocyte antigen (HLA) typing was performed. RESULTS: Histopathological examination of an explanted graft showed infiltration of T-lymphocytes and macrophages in the choroid and RPE, and an increased number of B-cell lymphocytes were found in the choroid. Indirect immunofluorescence showed weak RPE-choroid autoantibody immunoreactivity in three patients of different groups. Western blot did not show specific RPE-choroid autoantibody immunoreactivity and no difference of HLA genotypes between the groups was found. CONCLUSIONS: Although local mononuclear inflammatory cell infiltration and a high number of B-lymphocytes were observed in an explanted graft, we did not detect serological evidence of an autoimmune origin of the postoperative inflammation using direct immunofluorescence and Western Blot. Alternatively, the graft failure may have been caused by local innate inflammation, triggered by breakdown of tolerance. Based on our current findings of this small study group, we have no rationale to pursue therapies targeted towards autoreactive graft failure. More research is needed to confirm our findings.

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS IN A CASE OF PACHYCHOROID NEOVASCULOPATHY IN RETINITIS PIGMENTOSA.

PURPOSE: To report a rare case of pachychoroid neovasculopathy in retinitis pigmentosa (RP) and to describe its features and changes after treatment with bevacizumab as documented by swept-source optical coherence angiography. METHODS: A case report of a 69-year-old man with a history of RP who presented at our clinic with an acute decrease in visual acuity (Best corrected visual acuity) in his left eye. RESULTS: Upon the first examination, best-corrected visual acuity in the left eye was 20/50. Fundus examination and fundus autofluorescence showed bilaterally typical features of RP, and enhanced depth imaging-optical coherence tomography revealed a pachychoroid pattern. Fluorescein angiography and indocyanine green angiography suggested the presence of a choroidal neovascularization in the left eye, although no clear evidence of any neovascular network could be identified. Swept-source optical coherence angiography was performed, confirming the presence of a choroidal neovascularization network. The patient was treated with 2 monthly intravitreal injections of bevacizumab. After treatment, BVCA improved to 20/25, and no evidence of the vascular network was detectable on swept-source optical coherence angiography. CONCLUSION: Our case reports the uncommon association of RP with pachychoroid neovasculopathy. Swept-source optical coherence angiography proved to be a useful imaging technique for the diagnosis and follow-up of this condition. Intravitreal bevacizumab represents an effective treatment for choroidal neovascularization associated with RP.

Temporal variation of optical coherence tomography biomarkers as predictors of anti-VEGF treatment outcomes in diabetic macular edema.

PURPOSE: To report a longitudinal analysis of specific optical coherence tomography (OCT) features in eyes with diabetic macular edema (DME) treated with anti-VEGF. METHODS: A total of 133 eyes of 103 consecutive patients with center-involving DME were included in the study. The eyes were treated between August 2008 and April 2019 with three monthly intravitreal anti-VEGF injections, either with or without prompt or deferred laser, followed by pro re nata (PRN) re-treatment. The following OCT biomarkers were evaluated: subfoveal neuroretinal detachment (SND) (defined as present (SND+) or absent (SND-)), hyperreflective retinal foci (HRF) number (defined as: absent/few(HRF-) or moderate/many (HRF+)), external limiting membrane (ELM) integrity, central macular thickness (CMT), and central retinal thickness (CRT). Changes in SND status and in the number of HRF were evaluated at each DME recurrence throughout the follow-up(FU) period. Mutual correlation among OCT biomarkers and their relationship with visual and anatomic outcomes were assessed both at baseline and over the FU period. RESULTS: The mean FU was 71.2 months (SD 28.4; min. 12-max. 111). At baseline, the prevalence of SRD+ was 27.8% and a high number of HRF were detected in 41.4% of the eyes. A significant reduction in the number of HRF, CMT, CRT, and in the prevalence of SND was recorded in the post-loading phase (p-value <0.0001). In DME recurrences, the presence of SND+ and HRF+ was significantly more frequent in eyes with baseline SND+ and HRF+ compared to eyes presenting baseline SND- and HRF- (p-value <0.0001). No role of SND (p-value: 0.926) and HRF (p-value: 0.281) as baseline predictors of visual and anatomic outcomes was demonstrated, while a worse visual outcome was significantly correlated with a higher incidence of relapsing SND+ (p-value <0.0001) and HRF+ (p-value <0.0028) throughout the FU period. CONCLUSION: In this study, SND and HRF were frequently present in DME recurrences with the same pattern exhibited at baseline, suggesting that these OCT biomarkers may characterize a specific pattern of DME that repeats over time. Moreover, the results suggested that the persistence and recurrence of SND and HRF may account for a decrease in visual function more than the baseline prevalence of these biomarkers. Further studies are required to confirm these findings.

Intravitreal Brolucizumab for Neovascular Age-Related Macular Degeneration in a Vitrectomized Eye.

The efficacy of intravitreal anti-VEGF may be reduced in vitrectomized eyes due to accelerated drug clearance. Given its longer durability, brolucizumab may represent a suitable therapeutic option. However, its efficacy in vitrectomized eyes remains to be explored. Herein, we describe the management of a macular neovascularization (MNV) in a vitrectomized eye with brolucizumab after unsuccessful treatment with other anti-VEGF. A 68-year-old male was treated with pars plana vitrectomy for epiretinal membrane in his left eye (LE) in 2018. After surgery, best corrected visual acuity (BCVA) improved to 20/20 with a remarkable reduction of metamorphopsia. After 3 years, the patient returned, presenting visual loss in the LE due to MNV. He was treated with intravitreal bevacizumab injections. However, after the loading phase, an increased lesion size and exudation with worsening BCVA were detected. Therefore, the treatment was switched to aflibercept. However, after three monthly intravitreal injections, further worsening was recorded. Treatment was then switched to brolucizumab. Anatomical and functional improvement was noticed 1 month after the first brolucizumab injection. Two additional injections were performed, and further improvement was recorded with BCVA recovery to 20/20. At the last follow-up visit 2 months after the third injection, no recurrence was detected. In conclusion, determining whether anti-VEGF injections are efficacious for vitrectomized eyes would be helpful for ophthalmologists managing such patients, as well as when considering pars plana vitrectomy in eyes at risk of MNV. In our case, brolucizumab was found to be effective after unsuccessful treatment with other anti-VEGF. Additional studies are required to evaluate the safety and efficacy of brolucizumab for MNV in vitrectomized eyes.

LRG1 Expression Is Elevated in the Eyes of Patients with Neovascular Age-Related Macular Degeneration.

Leucine-rich a-2-glycoprotein 1 (LRG1) is a candidate therapeutic target for treating the neovascular form of age-related macular degeneration (nvAMD). In this study we examined the expression of LRG1 in eyes of nvAMD patients. Choroidal neovascular membranes (CNVMs) from patients who underwent submacular surgery for retinal pigment epithelium-choroid graft transplantation were collected from 5 nvAMD patients without any prior intravitreal anti-VEGF injection, and from six patients who received intravitreal anti-VEGF injections before surgery. As controls free of nvAMD, retina sections were obtained from the eyes resected from a patient with lacrimal sac tumor and from a patient with neuroblastoma. CNVMs were immunostained for CD34, LRG1, and α-smooth muscle actin (α-SMA). Aqueous humor samples were collected from 58 untreated-naïve nvAMD patients prior to the intravitreal injection of anti-VEGF and 51 age-matched cataract control patients, and LRG1 concentration was measured by ELISA. The level of LRG1 immunostaining is frequently high in both the endothelial cells of the blood vessels, and myofibroblasts in the surrounding tissue of CNVMs of treatment-naïve nvAMD patients. Furthermore, the average concentration of LRG1 was significantly higher in the aqueous humor of nvAMD patients than in controls. These observations provide a strong experimental basis and scientific rationale for the progression of a therapeutic anti-LRG1 monoclonal antibody into clinical trials with patients with nvAMD.

Microstructural Macular Changes after Pars Plana Vitrectomy for Primary Rhegmatogenous Retinal Detachment.

PURPOSE: This study aimed to describe foveal microstructural changes after pars plana vitrectomy (PPV) with air tamponade for rhegmatogenous retinal detachment (RRD). METHODS: External limiting membrane (ELM) and ellipsoid zone (EZ) integrity, cystoid macular edema (CME), and subretinal fluid bleb (SB) development were analyzed using optical coherence tomography in 59 eyes over a 6-month follow-up period after PPV surgery for RRD. Eyes were grouped as macula-on (n = 30) or macula-off (n = 29), and the association between ELM and EZ recovery and best-corrected visual acuity (BCVA) was investigated. Predictive factors for ELM and EZ recovery were also identified. RESULTS: The interval between symptom onset and surgery did not significantly differ between the macula-on and macula-off groups. Macula-on patients showed ELM and EZ integrity throughout, whereas macula-off patients had ELM and EZ integrity restored in 89.7% and 86.2% cases, respectively, with a resultant increase in final BCVA. Significant associations were found between preoperative macular involvement and ELM/EZ restoration. ELM/EZ recovery was also inversely associated with CME development. Significant associations were also found between final BCVA and preoperative BCVA and EZ recovery. CME and SB development were equally distributed between the 2 groups. CONCLUSION: Prompt surgery for macula-off RRD allows the progressive recovery of outer retinal layers and significant visual gain.

The prevalence of vitreomacular adhesion in eyes with macular oedema secondary to retinal vein occlusion selected for intravitreal injections.

PURPOSE: To assess the prevalence of vitreomacular adhesion (VMA) in consecutive naïve eyes diagnosed with macular oedema (ME) secondary to retinal vein occlusion (RVO) and to longitudinally evaluate the incidence of vitreomacular interface changes over time and the influence on response to treatment. DESIGN: Retrospective cross-sectional analysis and longitudinal cohort study conducted at two Italian tertiary referral centres. METHODS: A total of 295 eyes, treated with intravitreal ranibizumab and/or dexamethasone for ME secondary to RVO between June 2008 and May 2018, were enrolled in the study. 280 fellow eyes met the inclusion criteria and were included as control group. The vitreomacular interface status was evaluated by spectral domain optical coherence tomography (OCT) and graded according to the OCT-based International Classification System developed by the International Vitreomacular Traction Study (IVTS) group. RESULTS: At baseline, VMA was present in 130 (44.07%) RVO eyes and 142 (50.7%) control eyes (no statistically significant difference was found; p = 0.455). Mean follow-up (FU) was 35.98 months (min 6 - max 112). Throughout the FU, the incidence of spontaneous release of VMA (RVMA) in RVO eyes was significantly higher in comparison with that of the control group [59 (41.84%) RVO eyes versus 18 (12.33%) control eyes; p < 0.0001]. The number of injections in VMA+ eyes was significantly higher when compared with VMA- eyes. No significant difference was found between VMA+ and VMA- eyes regarding their mean best-corrected visual acuity (BCVA) at baseline and at each annual time point (p = 0.2). Differences in central macular thickness (CMT) were significant only at the baseline evaluation (p = 0.0303). CONCLUSIONS: Vitreomacular adhesion (VMA) was not found to be more prevalent in eyes with RVO compared to healthy fellow eyes, and RVO, in turn, did not result in a higher persistence of VMA over time. This suggests that VMA and RVO might be two independent retinal phenomena, with no mutual pathogenetic influence. Vitreomacular adhesion (VMA) might have an impact on the response to treatment, since it was found to result in a more intensive treatment regimen; however, it did not affect visual and anatomic outcomes. These results do not support vitrectomy or PVD induction in the prevention, nor the treatment, of RVO.

Retrobulbar triamcinolone for inflammatory choroidal neovascularization in pregnancy.

BACKGROUND: Choroidal neovascularization (CNV) in pregnancy has rarely been described. A differential diagnosis between inflammatory, idiopathic, and myopic CNV may be challenging. Moreover, there is no consensus on management, and therapeutic options may be further limited by patient and physician concerns about potential risk to the fetus. Herein, we report a case of inflammatory CNV during pregnancy and describe a previously unreported management approach with retrobulbar triamcinolone injections. CASE PRESENTATION: A 36-year-old woman presented with vision loss and metamorphopsia in her right eye while 21 weeks pregnant. She was diagnosed with an inflammatory CNV based on the following multimodal imaging findings: a type 2 lesion with the "pitchfork sign" on OCT, along with the absence of tomographic signs of myopic CNV, and the presence on autofluorescence of multiple hyper-autofluorescent spots, interpreted as focal areas of inflammation at the level of the outer retina and inner choroid. The patient refused oral corticosteroids and any intravitreal injection therapies. Therefore, she was treated with two trans-Tenon's retrobulbar injections of triamcinolone acetonide after explaining the procedure and acquiring consent. The treatment resulted in a regression of inflammatory signs and a reduction of neovascular activity. No adverse events occurred for the mother or the baby, neither during the pregnancy nor after delivery. CONCLUSION: Inflammatory CNV may be rarely associated with pregnancy. The correct diagnosis is crucial to allow the consideration of all possible management options. To the best of our knowledge, this is the first reported case of treatment with retrobulbar triamcinolone injections. This may represent a suitable therapeutic option in the absence of any other therapeutic approaches.

Biocompatibility of a Conjugated Polymer Retinal Prosthesis in the Domestic Pig.

The progressive degeneration of retinal photoreceptors is one of the most significant causes of blindness in humans. Conjugated polymers represent an attractive solution to the field of retinal prostheses, and a multi-layer fully organic prosthesis implanted subretinally in dystrophic Royal College of Surgeons (RCS) rats was able to rescue visual functions. As a step toward human translation, we report here the fabrication and in vivo testing of a similar device engineered to adapt to the human-like size of the eye of the domestic pig, an excellent animal paradigm to test therapeutic strategies for photoreceptors degeneration. The active conjugated polymers were layered onto two distinct passive substrates, namely electro-spun silk fibroin (ESF) and polyethylene terephthalate (PET). Naive pigs were implanted subretinally with the active device in one eye, while the contralateral eye was sham implanted with substrate only. Retinal morphology and functionality were assessed before and after surgery by means of in vivo optical coherence tomography and full-field electroretinogram (ff-ERG) analysis. After the sacrifice, the retina morphology and inflammatory markers were analyzed by immunohistochemistry of the excised retinas. Surprisingly, ESF-based prostheses caused a proliferative vitreoretinopathy with disappearance of the ff-ERG b-wave in the implanted eyes. In contrast, PET-based active devices did not evoke significant inflammatory responses. As expected, the subretinal implantation of both PET only and the PET-based prosthesis locally decreased the thickness of the outer nuclear layer due to local photoreceptor loss. However, while the implantation of the PET only substrate decreased the ff-ERG b-wave amplitude with respect to the pre-implant ERG, the eyes implanted with the active device fully preserved the ERG responses, indicating an active compensation of the surgery-induced photoreceptor loss. Our findings highlight the possibility of developing a new generation of conjugated polymer/PET-based prosthetic devices that are highly biocompatible and potentially suitable for subretinal implantation in patients suffering from degenerative blindness.

The Binding of CD93 to Multimerin-2 Promotes Choroidal Neovascularization.

Purpose: The purpose of this study was to investigate the involvement of CD93 and Multimerin-2 in three choroidal neovascularization (CNV) models and to evaluate their contribution in the neovascular progression of age-related macular degeneration (AMD). Methods: Choroidal neovascular membranes collected during surgery from AMD patients were analyzed by microscopy methods. Laser-induced CNV mouse models and choroid sprouting assays (CSAs) were carried out using the CD93 knockout mouse model. An original ex vivo CSA of vascular angiogenesis, employing choroid tissues isolated from human donors, was developed. Results: In contrast to healthy choroid endothelium, hyperproliferative choroidal endothelial cells (ECs) of AMD patients expressed high levels of CD93, and Multimerin-2 was abundantly deposited along the choroidal neovasculature. CD93 knockout mice showed a significant reduced neovascularization after laser photocoagulation, and their choroidal ECs displayed a decreased ability to produce sprouts in ex vivo angiogenesis assays. Moreover, the presence of an antibody able to hamper the CD93/Multimerin-2 interaction reduced vascular sprouting in the human CSA. Conclusions: Our results demonstrate that CD93 and its interaction with Multimerin-2 play an important role in pathological vascularization of the choroid, disclosing new possibilities for therapeutic intervention to neovascular AMD.

Subretinally injected semiconducting polymer nanoparticles rescue vision in a rat model of retinal dystrophy.

Inherited retinal dystrophies and late-stage age-related macular degeneration, for which treatments remain limited, are among the most prevalent causes of legal blindness. Retinal prostheses have been developed to stimulate the inner retinal network; however, lack of sensitivity and resolution, and the need for wiring or external cameras, have limited their application. Here we show that conjugated polymer nanoparticles (P3HT NPs) mediate light-evoked stimulation of retinal neurons and persistently rescue visual functions when subretinally injected in a rat model of retinitis pigmentosa. P3HT NPs spread out over the entire subretinal space and promote light-dependent activation of spared inner retinal neurons, recovering subcortical, cortical and behavioural visual responses in the absence of trophic effects or retinal inflammation. By conferring sustained light sensitivity to degenerate retinas after a single injection, and with the potential for high spatial resolution, P3HT NPs provide a new avenue in retinal prosthetics with potential applications not only in retinitis pigmentosa, but also in age-related macular degeneration.