Delaying anti-VEGF therapy during the COVID-19 pandemic: long-term impact on visual outcomes in patients with neovascular age-related macular degeneration.

OBJECTIVES: To evaluate the outcomes of delayed intravitreal injections (IVIs) caused by the outbreak of coronavirus disease 2019 (COVID-19), in patients with neovascular age-related macular degeneration (nAMD). METHODS: nAMD patients with scheduled IVIs between March 1st and April 30th, 2020 were stratified through a risk-based selection into a non-adherent group (NA-group) if they skipped at least one IVI and an adherent group (A-group) if they followed their treatment schedule. During the pandemic visit (v0), if a significant worsening of the disease was detected, a rescue therapy of three-monthly IVIs was performed. Multimodal imaging and best-corrected visual acuity (BCVA) findings were evaluated after 6 months (v6), compared between groups and with the visit prior the lockdown (v-1). RESULTS: Two hundred fifteen patients (132 females, mean age: 81.89 ± 5.98 years) delayed their scheduled IVI while 83 (53 females, mean age: 77.92 ± 6.06 years) adhered to their protocol. For both groups, BCVA at v0 was significantly worse than v-1 (mean 4.15 ± 7.24 ETDRS letters reduction for the NA-group and 3 ± 7.96 for the A-group) but remained stable at v6. The two groups did not significantly differ in BCVA trends after 6 months and neither for development of atrophy nor fibrosis. CONCLUSIONS: A risk-based selection strategy and a rescue therapy may limit the long-term outcomes of an interruption of the treatment protocol in patients with nAMD.

Ten-Year Incidence of Fibrosis and Risk Factors for Its Development in Neovascular Age-Related Macular Degeneration.

PURPOSE: To report the incidence and risk factors for fibrosis at 10 years in a large cohort of persons with neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective, multicenter, cohort study. METHODS: We included 225 naive nAMD eyes that underwent intravitreal anti-vascular endothelial growth factor treatment over 10 years of follow-up at two Italian referral centers. Demographic and clinical data were reviewed at baseline and on an annual basis. Onset of fibrosis was defined by clinically assessing photographs, fundus descriptions, or fluorescein angiograms. Optical coherence tomography (OCT) scans of fibrosis were inspected by an external reading center and graded as subretinal pigment epithelium (RPE), mixed, or subretinal. RESULTS: The mean age at baseline was of 72.1 ± 6.9 years. The incidence rate of fibrosis was estimated to be 8.9 per 100 person-years, with a cumulative incidence of 62.7% at 10 years. Fibrotic lesions were sub-RPE in 46.1%, mixed in 29.8%, and subretinal in 22.7%. Independent factors associated with fibrosis included the following: larger central subfield thickness variation (P < .001), submacular hemorrhages (P = .008), higher number of injections (P = .01), and worse baseline visual acuity (VA) (P = .03). Type 2 macular neovascularization was significantly associated with mixed and subretinal fibrosis. VA significantly declined over 10 years (-16.4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters), particularly in eyes with mixed and subretinal fibrosis (P < .001). CONCLUSIONS: We identified a 62.7% cumulative incidence of fibrosis in a large nAMD cohort at 10 years. Fibrosis was more common with frequent reactivations and lower baseline VA; its onset had a significant impact on final VA. This supports the hypothesis that nAMD patients should be promptly treated with proactive regimens.

Adaptive Optics of Kyrieleis Plaques in Varicella Zoster Virus-Associated Posterior Uveitis: A Multimodal Imaging Analysis.

Kyrieleis plaques (KP) represent a peculiar type of vasculitis affecting retinal arterial branches in a beaded segmental pattern that can be found in several posterior inflammatory ocular conditions. The nature and precise location of KP is unclear. Adaptive Optics (AO) provides an in vivo visualization of retinal vasculature on a microscopic level, thus permitting a more detailed characterization of KP as compared to traditional imaging techniques. This study aims to report AO imaging of KP in Varicella Zoster virus (VZV)-associated posterior uveitis and to correlate the findings with traditional imaging techniques. Three patients diagnosed with VZV posterior uveitis underwent adaptive optics (AO) imaging and traditional multimodal imaging techniques, including fundus photography, fluorescein angiography, indocyanine green angiography and optical coherence tomography. In all subjects, AO imaging revealed segmental hyporeflectivity confined to the vessel wall, with no evidence of arterial wall disruption or extravascular involvement. In our series, AO findings support the view that KP are localized within the inner arterial wall, possibly at the endothelial level.

Functional and anatomic changes between early postoperative recovery and long-term follow-up after combined epiretinal and internal limiting membrane peeling.

OBJECTIVE: To evaluate short- and long-term changes in best-corrected visual acuity (BCVA) and retinal layer thicknesses after combined epiretinal membrane (ERM) and internal limiting membrane (ILM) peeling for macular holes and symptomatic ERMs. DESIGN: Retrospective observational case series. PARTICIPANTS: Patients with ERMs or with macular holes and ERMs treated with combined ERM and ILM peeling. METHODS: Study eyes (n = 36) and healthy fellow eyes (n = 17) were evaluated using the automated segmentation of retinal layers performed by SPECTRALIS software that automatically calculated the average central retinal thickness and the average thickness in each of the individual retinal layers. The analysis was performed at 6-18 months after surgery and after 60 months. MAIN OUTCOME MEASURES: Changes in BCVA and retinal layer thicknesses determined by automated segmentation at the first and last follow-up visits. RESULTS: BCVA improved from a baseline 0.48 ± 0.25 logMAR (20/60 Snellen) to 0.18 ± 0.18 logMAR (20/30 Snellen) at the short-term postoperative examination (p < 0.0001). Between first and last follow-up visit, 5 eyes (14%) were classified as better, 28 (78%) as stable, and 3 (8%) as worse. BCVA of the control fellow eyes remained stable during the follow-up. The thicknesses of retinal layers decreased significantly (p < 0.009). At the last follow-up, the ganglion cell layer was thinner and the inner nuclear layer was thicker in the operated eyes compared with the healthy fellow eyes. CONCLUSION: Combined ERM and ILM peeling may improve BCVA in some patients. However, over a long follow-up period, it can be associated with progressive ganglion cell layer thinning that could affect BCVA stability.

Acute Retinal Necrosis: Clinical Features, Diagnostic Pitfalls, Treatment, and Outcome of an Insidious Disease in Children. Case Report and Review of the Literature.

Objective: This study aims to explore clinical features, diagnostic work-up, treatment, and outcomes of pediatric patients with acute retinal necrosis (ARN), and to propose a standardized management of this condition in childhood. Methods: Clinical manifestations, diagnostic work-up, and treatment of three pediatric cases with ARN were analyzed. Furthermore, a review of the literature was performed from January 1990 to November 2021, focused on 1) clinical presentation; 2) differential diagnosis, including both infectious and non-infectious conditions; 3) key role of diagnostic techniques; and 4) currently available treatments. Results: Data from 72 children with ARN (69 from literature and 3 from our center) were analyzed. The most frequent presenting symptoms were red eye resistant to topical treatment (57%) and altered vision (58%), 25 patients had bilateral involvement. In 30% a known history of herpetic infection was reported. PCR testing on anterior chamber and/or vitreous sampling was performed in 46 cases (64%) and was diagnostic in 88% of them, with herpes simplex virus (HSV) 2 being the most frequently identified pathogen (57%). All patients underwent systemic antiviral therapy (16% only oral); adjunctive intravitreal injections were performed in 21% of them. Conclusions: ARN is a rare but severe ocular infection presenting as a panuveitis with occlusive retinal vasculitis and peripheral retinal necrosis. Varicella-zoster virus and HSV 1-2 are most frequently implicated. Due to a high incidence of rhegmatogenous retinal detachment and optic atrophy, ARN has a poor prognosis with a potentially severe impact on visual function. Although a prompt recognition is crucial to prevent complications, ARN diagnosis in children is still challenging.

IMPACT OF CORONAVIRUS DISEASE PANDEMIC ON INTRAVITREAL INJECTIONS TREATMENT FOR MACULAR DISEASES: Report From a Referral Hospital in Milan.

PURPOSE: To describe our managing strategy for COVID-19 emergency, to evaluate the adherence to intravitreal treatment (AtT) rate during the outbreak in a referral hospital in Milan, and to correlate it with patients' clinical features. METHODS: The AtT rate of patients with scheduled intravitreal injections during the COVID-19 outbreak from February 23, 2020 to March 31, 2020 was compared with the previous trimester and with March 2019. The impact of age, sex, visual function, and diagnosis on the AtT rate during unlocked/locked weeks (from March 8th) was evaluated. RESULTS: Of 650 consecutive patients with scheduled intravitreal injections, the AtT rate during the COVID-19 outbreak was 0.37. This was significantly lower compared with AtT registered in the previous trimester (0.92) and in the same weeks in 2019 (0.90) (both P < 0.001). Patients adherent to treatment were significantly younger (P < 0.001) and had a lower best-corrected visual acuity in the fellow eye (P = 0.046). During the lockdown weeks, the AtT rate was significantly lower than in the two unlocked weeks (0.19 vs. 0.73, P < 0.001). In addition, the AtT rate in patients classified as "emergent" during the lockdown weeks was 0.60. CONCLUSION: These preliminary results can help the retina specialist community to foresee this unique scenario and to develop successful management strategies.