Optic neuritis following COVID-19 vaccination: Do autoimmune diseases play a role?

PURPOSE AND CONTEXT: We report two cases of optic neuritis following Pfizer-BioNTech COVID-19 vaccination in patients with autoimmune diseases. Post-vaccine optic neuritis, although rare, is reported in the literature and an autoimmune mechanism seems to be involved, especially in genetically predisposed subjects. METHOD: Report of two cases of optic neuritis following COVID-19 vaccination in patients with autoimmune diseases. KEY RESULTS: He novelty of this article is the fact that the two patients had a medical history of autoimmune diseases (Hashimoto thyroiditis and ankylosing spondylitis), a point of interest for research because it is not yet clear whether this could constitute a risk factor for adverse events after vaccination. CONCLUSIONS: The reactogenicity of COVID-19 mRNA vaccine in individuals suffering from immune-mediated diseases is yet to be elucidated and it is being increasingly investigated. Our paper supports the hypothesis that patients who are already affected or predisposed to autoimmune or autoinflammatory disorders should be carefully evaluated for the benefits and risks of COVID-19 mRNA vaccination.

Short-Term Outcomes of XEN45 Standalone versus Combined with Phacoemulsification in Open-Angle Glaucoma Patients: A Retrospective Study.

The XEN45 is a minimally invasive glaucoma surgery device commonly used in clinical practice. This retrospective study included consecutive patients with open-angle glaucoma who underwent a XEN45 implant with mitomycin C, either alone or in combination with phacoemulsification, between June 2015 and March 2021. The primary end point was the mean change in intraocular pressure (IOP) from the baseline to month 6. A total of 677 eyes, 395 (58.3%) in the XEN alone group and 282 (41.7%) in the XEN+Phaco group, were included in this study. The preoperative IOP was significantly lowered from 28.7 ± 8.6 mmHg and 25.4 ± 6.9 mmHg to 13.5 ± 5.0 mmHg and 13.5 ± 4.1 mmHg at month 6 in the XEN solo and XEN+Phaco groups, respectively, with p < 0.0001 each. The mean (95% confidence interval) number of ocular hypotensive medications was significantly reduced from 3.3 (3.2-3.4) to 0.2 (0.1-0.2) and from 3.1 (2.9-3.2) to 0.2 (0.1-0.2) in the XEN solo and XEN+Phaco groups, respectively, with p < 0.0001 each. Needling was performed in 228 (33.7%) eyes. Conclusions: the XEN implant significantly reduces both IOP and the number of ocular hypotensive medications. IOP lowering was higher in the XEN solo group than in the XEN+Phaco one, although such a difference was only evident during the first month after surgery.

Oxidative stress in retinal pigment epithelium impairs stem cells: a vicious cycle in age-related macular degeneration.

Aging, chronic oxidative stress, and inflammation are major pathogenic factors in the development and progression of age-related macular degeneration (AMD) with the loss of retinal pigment epithelium (RPE). The human RPE contains a subpopulation of progenitors (i.e., RPE stem cells-RPESCs) whose role in the RPE homeostasis is under investigation. We evaluated the paracrine effects of mature RPE cells exposed to oxidative stress (H2O2) on RPESCs behavior through co-cultural, morphofunctional, and bioinformatic approaches. RPESCs showed a decline in proliferation, an increase of the senescence-associated ß-galactosidase activity, the acquisition of a senescent-like secretory phenotype (SASP), and the reduction of their stemness and differentiation competencies. IL-6 and Superoxide Dismutase 2 (SOD2) seem to be key molecules in RPESCs response to oxidative stress. Our results get insight into stress-induced senescent-associated molecular mechanisms implicated in AMD pathogenesis. The presence of chronic oxidative stress in the microenvironment reduces the RPESCs abilities, inducing and/or maintaining a pro-inflammatory retinal milieu that in turn could affect AMD onset and progression.

Sclerochoroidal calcification as an incidental finding during oncological staging of a patient with parotid malignancy: A case report.

INTRODUCTION: Incidental finding of mass lesion in the choroid represents a very challenging situation for the ophthalmologist. We describe a case of an incidental, computed tomography (CT)-hyperintense, choroidal lesion in a patient with parotid malignancy and renal failure, and how multimodal imaging helped us reaching the correct diagnosis. CASE DESCRIPTION: A 63-year-old man with parotid gland malignancy was brought to our attention because preoperative staging CT showed a hyperintense choroidal lesion of the right eye. Fundus examination showed a yellow elevated lesion near the superior temporal branch retinal artery. Enhanced depth imaging optical coherence tomography (EDI-OCT), A- and B-scan ultrasonography, and Indocyanine Green Angiography (ICGA) allowed us to exclude a malignant lesion and to diagnose a sclerochoroidal calcification. CONCLUSION: Multimodal imaging can guide the clinician to choose the appropriate therapeutic approach even in case of uncommon conditions like sclerochoroidal calcification.

Retinal obliterative vasculitis associated to contralateral retinal neovascularization in membranoproliferative glomerulonephritis.

PURPOSE: To report our experience with a peculiar case of asynchronous bilateral retinal vascular occlusion in a patient suffering from membranoproliferative glomerulonephritis. CASE REPORT: A 57-year-old dialysed male affected by membranoproliferative glomerulonephritis who underwent kidney transplantation complained of a sudden vision loss in his right eye (RE). His best-corrected visual acuity (BCVA) was 20/40 in RE and 20/20 in the left eye (LE); ophthalmological and fluorangiographic examinations revealed unilateral retinal obliterative vasculitis with panuveitis and apparent sparing of contralateral eye. About 6 months later the patient developed a branch retinal vein occlusion associated with a papillary neovascular membrane in LE. Corticosteroid therapy was administered and immunosuppressant dosage was increased with macular oedema reduction in both events. CONCLUSION: We report a case of unilateral retinal obliterative vasculitis and subsequent contralateral retinal neovascularization and branch retinal vein occlusion in a patient affected by membranoproliferative glomerulonephritis.

Punctate inner choroidopathy reactivation following COVID-19: A case report.

PURPOSE: The purpose of this study is to report our experience with a case of punctate inner choroidopathy (PIC) reactivation following COVID-19. CASE REPORT: A 29-year-old caucasian woman with past ophthalmological history of bilateral PIC reported sudden visual acuity decrease in her right eye (RE) 3 weeks after SARS-CoV-2 infection. Her best-corrected visual acuity (BCVA) was 20/32 in RE; fundus examination and multimodal imaging (including indocyanine-green angiography, fundus autofluorescence, and optical coherence tomography) was consistent with unilateral PIC reactivation. The active choroidal lesions responded to high-dose corticosteroids, with functional improvement. CONCLUSION: Sars-CoV-2 infection could induce autoimmune and autoinflammatory dysregulation in genetically predisposed subjects. We report a case of PIC reactivation following COVID-19.

Intraocular Pressure Rise Linked to Silicone Oil in Retinal Surgery: A Review.

Silicone oil represents the main choice for intraocular tamponade in cases of complicated retinal detachment surgery. The intraocular pressure of an eye filled with silicone oil could increase, driven by a variety of different forces, according to several mechanisms. Two main conditions have been highlighted, depending on the onset: early hypertension or late glaucoma. The different types of silicone oils and their physico-chemical properties are varied and may play a role in the determination of intraocular pressure rise. The current body of literature allows for the illustration and categorization of the incidence and risk factors, as well as the pathogenesis and the management of the early postoperative hypertension subtended by an open- and closed-angle, along with the late onset silicone oil-induced glaucoma. Understanding the leading actors on the stage of ocular pressure elevation concurrently with silicone oil application for retinal surgery could help in guiding the timely and appropriate course of treatment.

EX-PRESS Glaucoma Filtration Device: Management of Complications.

The EX-PRESS glaucoma filtration device appears to be an effective addition to our options to treat refractory glaucoma. The possibility to create a sclerostomy without tissue excision provides a safe and reliable outflow pathway for aqueous that is standard in size, reducing much of the variability associated with a surgical procedure. Prospective randomized studies comparing EX-PRESS implantation with trabeculectomy show encouraging results. However, complications usually encountered in filtration surgery have been reported, and EX-PRESS implantation can also lead to specific device-related complications. This article reviews the most common complications associated with this procedure.

Development and preliminary validation of the Behçet's syndrome Overall Damage Index (BODI).

OBJECTIVE: To develop and validate the evidence-based and consensus-based Behçet's Syndrome Overall Damage Index (BODI). METHODS: Starting from 120 literature-retrieved preliminary items, the BODI underwent multiple Delphi rounds with an international multidisciplinary panel consisting of rheumatologists, internists, ophthalmologists, neurologists, and patient delegates until consensus was reached on the final content. The BODI was validated in a cross-sectional multicentre cohort of 228 patients with Behçet's syndrome (BS) through the study of (a) correlation between BODI and Vasculitis Damage Index (VDI) and (b) correlation between BODI and disease activity measures (ie, Behçet's Disease Current Activity Form (BDCAF), Physician Global Assessment (PGA), Patient Global Assessment (PtGA)), c) content and face validity and (d) feasibility. RESULTS: The final BODI consists of 4 overarching principles and 46 unweighted-items grouped into 9 organ domains. It showed good to excellent reliability, with a mean Cohen's k of 0.84 (95% CI 0.78 to 0.90) and a mean intra-class correlation coefficient of 0.88 (95% CI 0.80 to 0.95). Overall, 128 (56.1%) patients had a BODI score ≥1, with a median score of 1.0 (range 0-14). The BODI significantly correlated with the VDI (r=0.693, p<0.001), demonstrating to effectively measure damage (construct validity), but had greater sensitivity in identifying major organ damage and did not correlate with disease activity measures (ie, BDCAF: p=0.807, PGA: p=0.820, PtGA: p=0.794) discriminating damage from the major confounding factor. The instrument was deemed credible (face validity), complete (content validity) and feasible by an independent group of clinicians. CONCLUSIONS: Pending further validation, the BODI may be used to assess organ damage in patients with BS in the context of observational and controlled trials.

Photodynamic therapy and subthreshold micropulse laser treatment - A novel combined approach for the treatment of serous retinal detachment in dome-shaped macula.

Dome-shaped macula (DSM) is characterized by an inward convexity of the macula in myopic eyes, as visualized on optical coherence tomography (OCT). Serous retinal detachment (SRD) is a common complication of DSM, leading to a deterioration of visual acuity, in association with retinal pigment epithelium (RPE) atrophic changes. Many different therapeutic approaches to SRD secondary to DSM have been attempted, with variable results. We report our experience (11 treatment-naïve patients) with a combined new treatment approach, using half-fluence and half-dose photodynamic therapy (PDT) followed by subthreshold 577 nm micropulse laser treatment (STLT), for SRD related to DSM after a 6-month follow-up. Central foveal thickness was significantly decreased at the end of the follow-up. SRD diminished in all cases, and 5 eyes (45.4 %) registered complete resolution at the end of the 6-month follow-up, while 6 eyes (54.5 %) experienced two lines of improvement in BCVA at the end of the follow-up. No case showed postoperative complications. Therefore, this represents the first study evaluating the visual and anatomical outcomes of a safe and effective combined treatment of SRD in DSM.

Long-term improvement of retinal sensitivity after macular hole surgery over at least 9-year-old follow-up: a case series.

PURPOSE: To evaluate the correlations between anatomical and functional changes in idiopathic macular hole (IMH) surgery in long-term follow-up. METHODS: This is a prospective, interventional single centre case series. The final sample is formed by 14 eyes of 14 patients who had undergone IMH surgery in our institution between 2005 and 2009 and were still followed up in 2019. Reported data were pre- and post-operative best-corrected visual acuity (BCVA), retinal sensitivity and fixation stability values on MP-1 and structural macular features on spectral domain optical coherence tomography. Optical coherence tomography angiography (OCTA) was utilized to assess microvascular characteristics at the final visit. Only patients with a successful MH closure were enrolled, excluding eyes affected by other relevant pathologies. RESULTS: Mean BCVA improvement was significant after surgery (t test, p value < 0.001) and presented a slight, not statistically significant raise, between the post-operative and long-term follow-up. Differently, mean retinal sensibility (dB) showed a highly statistically significant difference between pre-operative and post-operative (t test, p value = .002) and post-operative and last follow-up (p value < 0.001). In the long-term follow-up, subjects having integrity of the inner segment/outer segment (IS/OS) layer showed no statistically significant difference in BCVA compared with subjects with IS/OS discontinuity (t test, p value = 0.72). OCTA parameters of the operated eye showed no statistical significance compared with the fellow eye. CONCLUSIONS: In successfully closed MHs, retinal sensibility measured by microperimetry significatively increases after a long follow-up period even when BCVA remains stable or raises slightly. Vessel density organization tends to be quantitatively similar to fellow eye several years after surgery.

Intraocular Inflammation Control and Changes in Retinal and Choroidal Architecture in Refractory Non-Infectious Uveitis Patients after Adalimumab Therapy.

Background: Non-infectious uveitis represents a leading cause of visual impairment, and inflammation control represents a major priority in tackling visual acuity loss due to complications such as macular edema; different immunomodulatory drugs are currently being used, including anti-TNF-alpha Adalimumab. Methods: This was a monocentric observational study of 18 eyes of 18 patients with non-infectious uveitis treated with Adalimumab. The primary endpoint was the control of ocular inflammation. The secondary endpoints included the study of macular and choroidal thickness and architecture, visual acuity, changes in other treatments, and adverse effects. Results: Ocular inflammation was controlled at 12 months for 83.3% of patients. Central macular thickness improved from a median of 229.75 µm at baseline to 213 µm at 12 months, while choroidal thickness decreased by 11.54% at the end of the follow-up. A reduction of vasculitis on fluorescein angiography and of hyperreflective spots on optical coherence tomography was noted. Visual acuity also improved from 0.51 (logMAR) before treatment to 0.24 at more than 12 months (p = 0.01). A total of 11.1% of patients experienced side effects. Conclusion: Our study confirms the efficacy of adalimumab for the control of ocular inflammation, visual acuity preservation, and for corticosteroid sparing.

Papillary Vessel Density Changes After Intravitreal Anti-VEGF Injections in Hypertensive Patients with Central Retinal Vein Occlusion: An Angio-OCT Study.

PURPOSE: To investigate papillary microvascular changes in patients affected by macular edema due to Central Retinal Vein Occlusions (CRVO) after anti-Vascular Endothelial Growth Factor (VEGF) therapy. METHODS: Prospective analysis of papillary and peripapillary vessel density (VD) changes in 18 eyes of 18 hypertensive patients affected by CRVO before and after the loading-phase of intravitreal Ranibizumab (IVR) injections. Data were quantitatively measured by optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) before as well as 1 month and 4 months after injections. The correlation between post-treatment best-corrected visual acuity (BCVA) and changes in the retinal microvasculature evaluated by OCTA was assessed. Results: 18 eyes of 18 consecutive patients with a known history of arterial hypertension and affected by an acute CRVO episode were enrolled. Central macular thickness (CMT) was significantly reduced after IVR injections (p < 0.001), while mean BCVA improved from 0.70 ± 0.26 logarithm of the minimal angle of resolution (logMAR) units at baseline to 0.25 ± 0.18 logMAR units after 4 months (p < 0.001). VD inside disc and peripapillary significantly increased (p < 0.001 and p = 0.01, respectively) after treatment. CONCLUSIONS: OCTA showed VD increase in the papillary area in patients affected by CRVO after anti-VEGF therapy. This area could represent a new region of interest to study microvasculature changes concomitant with severe macular edema.

The Eye as a Window to Systemic Infectious Diseases: Old Enemies, New Imaging.

BACKGROUND: Syphilis, tuberculosis and toxoplasmosis are major infectious diseases worldwide; all of them are multisystem pathologies and share a possible ocular involvement. In this context, a fundamental help for the definitive diagnosis is provided by the ophthalmologist, through clinical evaluation and with the aid of a multimodal imaging examination. METHODS: We hereby describe selected cases who came to our attention and were visited in our eye clinic. In all clinics, the use of retinal and optic disc multimodal imaging during ophthalmological evaluation allowed to make a diagnosis of an infectious disease. RESULTS: In our tertiary referral center more than 60 patients with syphilis, tuberculosis and toxoplasmosis have been evaluated in the last two years: In 60% of cases the ophthalmological evaluation was secondary to a previous diagnosis of an infectious disease, while in the remaining cases the ophthalmologist, with the help of a multimodal imaging examination and clinical evaluation, represented the physician who leads to the diagnosis. CONCLUSION: Our results confirm how in these life-threatening pathologies a prompt diagnosis is mandatory and may benefit from a multidisciplinary and multimodal imaging approach, especially during ophthalmological evaluation.

Multimodal Imaging Analysis of Acute Syphilitic Posterior Placoid Chorioretinitis: A Case Report.

The authors report a multimodal imaging analysis of a case of acute syphilitic posterior placoid chorioretinitis (ASPPC) occurring in a 51-year-old man. Best-corrected visual acuity (BCVA) was 0.5 and 0.8 in the right and left eyes, respectively. The authors performed spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and indocyanine green angiography. All of the examinations were suggestive of the diagnosis of ASPPC, a rare manifestation of syphilis that has distinctive anatomical characteristics that are detectable early on with multimodal imaging. Moreover, serological tests were positive for syphilis infection, so the patient received intravenous penicillin G for 14 days. Final BCVA was 1.0 in the right eye and 0.9 in the left eye. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e179-e184.].

Flare changes after intravitreal injection of ocriplasmin in symptomatic vitreomacular traction syndrome.

PURPOSE: To evaluate the changes in anterior chamber flare after a single intravitreal injection of ocriplasmin (125 µg), in patients with symptomatic vitreomacular traction syndrome (VMT). STUDY DESIGN: An institutional review board-approved single-center not randomized prospective study. METHODS: Fifteen eyes of fifteen patients (9 women, 6 men) underwent intravitreal injection with ocriplasmin for symptomatic VMT (width of attachment ≤ 1500 µm). Anterior segment flare was measured with a laser flare meter (Kowa) before intravitreal injection and 1 day, 1 week, 1 month after injection. The changes in flare were analyzed; the resolution of VMT was evaluated with spectral-domain OCT. RESULTS: The mean anterior chamber flare was 10.5 ± 1.9 photons per millisecond (photons/ms) before the injection. After 1 day it increased to 13.6 ± 2.7 photons/ms (p = 0.027) and after 1 week to 14.4 ± 2.5 photons/ms (p = 0.005); after 1 month it decreased to 12.3 ± 2.3 photons/ms (p = 0.123). At 1 day and 1 week after injection, mean anterior chamber flare of fellow eyes was significantly lower than study eyes, while at 1 month this difference was not significant (12.3 ± 2.3 vs. 10.5 ± 1.8 photons/ms, p = 0.124, for study and fellow eyes). There was no statistically significant difference in the changes in flare between women and men or between phakic (N = 10) and pseudophakic (N = 5) eyes. No eye demonstrated intraretinal damage at any time-point. Also, 9 eyes showed resolution of VMT while 6 eyes demonstrated persistence of VMT. CONCLUSION: Our study shows that intravitreal injection of ocriplasmin can be a safe and effective approach to treat symptomatic VMT syndrome in selected patients.

Effects of senescent secretory phenotype acquisition on human retinal pigment epithelial stem cells.

Regenerative medicine approaches based on mesenchymal stem cells (MSCs) are being investigated to treat several aging-associated diseases, including age-related macular degeneration (AMD). Loss of retinal pigment epithelium (RPE) cells occurs early in AMD, and their transplant has the potential to slow disease progression.The human RPE contains a subpopulation of cells - adult RPE stem cells (RPESCs) - that are capable of self-renewal and of differentiating into RPE cells in vitro. However, age-related MSC changes involve loss of function and acquisition of a senescence-associated secretory phenotype (SASP), which can contribute to the maintenance of a chronic state of low-grade inflammation in tissues and organs.In a previous study we isolated, characterized, and differentiated RPESCs. Here, we induced replicative senescence in RPESCs and tested their acquisition of the senescence phenotype and the SASP as well as the differentiation ability of young and senescent RPESCs.Senescent RPESCs showed a significantly reduced proliferation ability, high senescence-associated ß-galactosidase activity, and SASP acquisition. RPE-specific genes were downregulated and p21 and p53 protein expression was upregulated.These findings document the effects of senescence and SASP acquisition on RPESC differentiation ability and highlight the need for a greater understanding of their role in AMD pathogenesis.

PERIPAPILLARY RETINAL NERVE FIBER THICKNESS CHANGES AFTER VITRECTOMY FOR EPIRETINAL MEMBRANE IN EYES WITH AND WITHOUT VITREOUS DETACHMENT.

PURPOSE: To compare the changes in postoperative peripapillary retinal nerve fiber layer (p-RNFL) thickness after vitrectomy for epiretinal membrane in eyes with preexisting posterior vitreous detachment (PVD) and eyes with surgically induced PVD. METHODS: This study included consecutive patients who underwent 25-gauge vitrectomy for epiretinal membrane. Eyes were divided, according to intraoperative PVD status, into a preexisting PVD group and surgically induced PVD group. Best-corrected visual acuity, p-RNFL thickness, and central retinal thickness were performed before and at 1, 3, and 6 months after surgery. RESULTS: One hundred and twenty eyes of 120 patients were enrolled: 64 eyes in the preexisting PVD group and 56 eyes in the surgically induced PVD group. In the preexisting PVD group at 6 months, the mean global p-RNFL thickness did not change, whereas it was reduced in the temporal sector (P = 0.034). In the surgically induced PVD group at 6 months, significant decreases were observed in global p-RNFL thickness (P = 0.027), temporal (P = 0.021), temporal inferior (P = 0.030), and nasal inferior sectors (P = 0.010). At 6 months, the two groups differed significantly in temporal (P < 0.001) and temporal inferior sectors (P = 0.004). The preoperative mean best-corrected visual acuity improved significantly at 6 months in both groups. CONCLUSION: Postoperative p-RNFL thickness after vitrectomy for epiretinal membrane tended to decrease in the temporal sector in all eyes and in the temporal inferior and nasal inferior sectors in eyes with surgically induced PVD.

Acute macular neuroretinopathy associated with subclinical cytomegalovirus infection.

PURPOSE: To report a case of bilateral acute macular neuroretinopathy (AMN) occurring in a 32-year-old woman, analyzed using the multimodal imaging technique. CASE REPORT: A 32-year-old Caucasian woman presented with 20 days history of acute onset of blurred vision in the right eye. The best-corrected visual acuity (BCVA) was 0.8 and 1.0 in the right and left eyes, respectively. She reported a lower urinary tract infection associated with fever, 7 days before the onset of the ocular symptoms. Serological tests demonstrated the presence of IgM specific for cytomegalovirus (CMV), while all the other laboratory tests were negative. SD-OCT exhibited the disruption of the inner segment-outer segment junction, associated with hyper-reflectivity of a thickened outer plexiform layer overlying such area associated with thinning of the outer nuclear layer. The patient was diagnosed with AMN and received a corticosteroid treatment. During all the follow-up, OCT features did not change, although BCVA improved. Four months after the first visit, we found also in the left eye a subfoveal IS/OS disruption but differently from the right eye, in which the abnormalities persisted during all the follow-up visits, in the left one they disappeared only after a month. The IgM specific for the CMV remained positive during the whole follow-up. CONCLUSIONS: To our knowledge, this is the first patient reported with a diagnosis of AMN associated with persisting presence of IgM specific for CMV.

Biologic Therapy in Inflammatory Eye Conditions (Ophtalmology): Safety Profile.

Non-infectious uveitis can be a potentially sight threatening disease. Very recently, therapeutic strategies have turned towards a new methodology, which includes biologic agents. The introduction of biologic drugs has started a Copernican revolution in ophthalmology: biologic therapies represent a revolutionary option for those patients who present non-responder, sight threatening uveitis. The availability of these therapies has improved the uveitis outcome. The present review shows the most relevant medical literature on biologic agents in ophthalmology, such as tumor necrosis factor blockers, anti-interleukins and other related biologics. Several papers reported the efficacy of biologic agents in a large number of refractory uveitides, which suggest a promising role of biologic drugs for selected cases. On the other hand, the medical literature does not have consistent numbers yet, which hopefully will validate the promising preliminary results. Biologic agents are not only promising drugs for the treatment of nonresponder uveitis, but also they show an apparently favourable safety profile, although several topics remain unsolved: it is still not clear when commencing the treatment, which agent to choose, and the length of biologic therapy. Moreover, the high costs and the still not clear safety profile have very often limited their use only for severe, non-responder uveitis in highly specialized uveitis centres.