Intravitreal Dexamethasone as a Rescue for Anti-Vascular Endothelial Growth Factor Therapy in Neovascular Age-Related Macular Degeneration with Persistent Disease Activity and High Treatment Demand.

Purpose: To assess the impact of switching to, or adding, an intravitreal dexamethasone implant (Dex; Ozurdex®) in anti-vascular endothelial growth factor (VEGF) therapy on disease stability and treatment intervals in eyes with neovascular age-related macular degeneration (nAMD) and persistent disease activity and high treatment demand. Methods: This retrospective noncomparative multicenter longitudinal case series included pseudophakic eyes with nAMD and persistent retinal fluid despite regular anti-VEGF therapy (ranibizumab or aflibercept) that received at least 1 intravitreal Dex implant. Visual acuity, central retinal thickness (CRT), and intraocular pressure were recorded before, and after, the addition of Dex to anti-VEGF therapy. Results: Sixteen eyes of 16 patients met the inclusion criteria of persistent fluid despite anti-VEGF therapy, under treatment intervals of ≤7 weeks in 14 instances. Patients were 80.9 ± 7.4 years old and had received 25.5 ± 17.4 anti-VEGF injections before Dex over a period of 36.4 ± 21.9 months before switching. The treatment interval increased from 5.5 ± 3.2 weeks between the last anti-VEGF and first Dex injection to 11.7 ± 7.3 weeks thereafter (P = 0.022). CRT remained stable (385.3 ± 152.1, 383.9 ± 129.7, and 458.3 ± 155.2 µm before switching as well as 12 and 24 months after switching; P = 0.78 and P = 0.36, respectively). An insignificant mean short-term early increase in visual acuity was not sustained over time. Conclusions: The addition of Dex resulted in a relevant and sustained increase in treatment intervals, whereas CRT and visual acuity remained stable in these difficult-to-treat eyes. It may be discussed whether inflammation or other steroid-responsive factors play a significant role in cases of nAMD with nonsatisfactory responses to anti-VEGF.

Preventive Inflammation Management with Steroids before Retreatment with Anti-VEGF after Severe Inflammation due to Brolucizumab.

PURPOSE: We report two successful cases of treatment by steroids after severe inflammation due to an intravitreal injection (IVI) of brolucizumab and their retreatment with another type of anti-vascular endothelial growth factor (VEGF), with steroid treatments to prevent severe inflammatory recurrence in patients with exudative age-related macular degeneration (AMD). CLINICAL CASES, CASE 1: An 88-year-old woman with exudative AMD in her left eye who had persistent subretinal fluid despite receiving an IVI, including ranibizumab and, subsequently, aflibercept. A switch to brolucizumab was decided. Two weeks after the third dose, she had a visual loss decreasing from 20/40 to counting fingers at 50 cm. Fundus examination revealed retinal whitening and perivenous sheathing. Fluoresceine angiography confirmed retinal arterial occlusion. Differential diagnoses were ruled out. She was treated with intravenous methylprednisolone and prednisolone eye drops. Three months after the treatment, visual acuity improved to 20/80 with no intraocular inflammation but subretinal fluid recurred. IVI of ranibizumab was rescheduled with preventive treatment by oral and local prednisolone without any inflammation recurrence. CASE 2: An 80-year-old man with exudative AMD in his right eye who had persistent subretinal fluid despite an IVI of aflibercept. Switching him to brolucizumab was decided. Two months after the third dose, he had blurred vision with no pain. Visual acuity decreased from 20/20 to 20/25. Examination showed 1+ anterior chamber cells and hyalitis. We confirmed the diagnosis of anterior uveitis with hyalitis. Differential diagnoses were ruled out. Treatment by prednisolone eye drops was initiated every 30 minutes for 1 day with a gradual decrease for 6 weeks. One week later, visual acuity improved to 20/20 with no inflammation. Three weeks later, subretinal fluid due to AMD increased. The patient was retreated by aflibercept with prednisolone eye drops, 48 hours before and after the IVI, with no recurrence of inflammation. DISCUSSION: Brolucizumab is one of the latest FDA-approved anti-VEGF agents for wet AMD. Since its wider use, few cases of severe ocular inflammation have been reported in post-marketing analysis. Because wet AMD recurrences should be expected after intraocular inflammation, insight is needed into treatment tolerance in cases that received further IVI retreatment. CONCLUSION: Our cases demonstrate that an IVI reinjection with a different anti-VEGF drug for exudative AMD recurrence can be safely reperformed. The use of local steroids could be effective in preventing recurrence of ocular inflammation after severe intraocular inflammation due to brolucizumab.

Patient Perspective on the Monitoring of Their Wet Age-Related Macular Degeneration during Coronavirus Disease 2019: A Retrospective Study.

Background and Objectives: The purpose was to provide the patients' perspective on the monitoring of their wet age-related macular degeneration (wet AMD) during coronavirus disease 2019 (COVID-19) and the importance of telemedicine. Materials and Methods: Wet AMD patients that underwent intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in two Swiss ophthalmology clinics, completed two questionnaires after the first confinement due to COVID-19 in Switzerland. The first evaluated their views concerning their adherence to scheduled injections during the confinement, and the application of telemedicine in the future. The second, adapted from the National Eye Institute Visual Function Questionnaire-25, assessed their opinions on visual function change during confinement. Results: From a total of 130 patients, 8.5% responded they did not respect their assigned schedule (group 1) while 91.5% responded they did (group 2). A total of 78.7% of group 2 considered treatment reception as more relevant compared to the risk of COVID-19 contraction. During the pre-lockdown period, group 2 patients required more help from others than group 1 patients (p = 0.02). In the possibility of another lockdown, 36.3% of group 1 and 8.7% of group 2 would choose telemedicine to monitor their wet AMD (p = 0.02), 54.5% and 86.9% would rather visit the clinic (p = 0.02), while 9.0% and 4.3% would cancel their appointment, respectively. It was found that 70% of group 1 and 33.6% of group 2 would prefer to use the telemedicine services than visiting a telemedicine centre (p = 0.04). Conclusions: During circumstances similar to the COVID-19 confinement, most patients would prefer to visit the clinic. Group 1 would prefer wet AMD monitoring via telemedicine at a higher rate than group 2.

Six Cases of Retinal Vascular Anomalies after Coronavirus Disease 2019: A Case Series.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) and its rapid spread has resulted in unexplored clinical ophthalmological manifestations. This report aims to describe a series of retinal vascular anomalies diagnosed with the use of fluorescein angiography, following contraction of COVID-19. HISTORY AND SIGNS: Symptoms reported by patients were central scotoma (one case), inferior scotoma (one case), and a sensation of mild loss of vision during the COVID-19 follow-up (four cases). Best-corrected visual acuity was preserved in all patients, apart from one, who had a visual acuity of 0.4, decimal scale (6/15, Snellen) in the left eye. THERAPY AND OUTCOME: Clinical manifestations included bilateral retinal vasculitis (two cases), branch retinal vein occlusion (one case), branch retinal artery occlusion (one case), hemi-central retinal vein occlusion (one case), and optic disc edema due to central retinal vein occlusion (one case) occurring 0 - 8 months after COVID-19 contraction. Serological testing was performed in every patient to exclude any other recognized cause of retinal vascular occlusion and inflammation and to confirm immunity against the novel coronavirus. None of the patients required any ocular treatment. CONCLUSIONS: Arterial and venous occlusive as well as inflammatory retinal vascular pathologies can occur both during and after the acute phase of COVID-19 as manifestations of ocular long-term effects of COVID-19 and should be included in the differential diagnosis of retinal occlusive pathologies. This case series suggests that careful investigations, including fundoscopy and fluorescein angiography, should be required in patients with visual complaints, both in the acute and long-term follow-up of COVID-19.

Prediction of Postoperative Visual Outcome in Patients with Idiopathic Epiretinal Membrane.

PURPOSE: The aim of this study was to estimate the association between preoperative characteristics in subjects with idiopathic epiretinal membrane (ERM) and visual acuity improvement after vitrectomy and create an algorithm for predicting postoperative visual outcome. METHODS: In a retrospective, cross-sectional study, we included adults with idiopathic ERM and excluded subjects with low-quality scans, other ocular conditions, and previous surgery except cataract surgery. Baseline characteristics were extracted from medical files, spectral-domain OCT, and OCT angiography. Visual improvement was expressed as a binary variable. RESULTS: Fifty-four subjects were included in the study. Three months postoperatively, 30 subjects improved, 10 remained stable, and 14 deteriorated. Spearman correlation showed no correlation between variables and visual acuity improvement (<0.39). Reduced dimensionality showed that baseline visual acuity, lens status, foveal aspect, spherical equivalent, and 2 interactive variables including foveal aspect and lens status have the strongest effect on improvement. Five-fold logistic regression based on these variables provided a model with AUC 0.9 ± 0.06. CONCLUSION: No variable has a direct predictive role on visual acuity improvement; however, baseline visual acuity, lens status, foveal aspect and spherical equivalent, when combined, provide a predictive model that could serve as a tool for more informed decisions.

FOVEA PLANA ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY: New Perspectives.

PURPOSE: To report on the reliability of optical coherence tomography angiography (OCTA) to diagnose fovea plana. METHODS: A retrospective, cross-sectional, case-control study included patients with foveal persistence of the inner retinal layers, confirmed by spectral domain OCT, and superficial capillary plexus (SCP) and deep capillary plexus foveal vascularization confirmed by OCTA. A healthy control group was selected. The best-corrected visual acuity was obtained. Spectral-domain OCT was used for measuring the outer nuclear layer thickness, and OCTA determined the foveal avascular zone, SCP, and deep capillary plexus vascular density. RESULTS: Optical coherence tomography angiography reliability, based on all parameters, reached 97%, whereas based only on SCP vascular density 91%. The plana group (n = 57) differed significantly from the control group (n = 28) in terms of foveal avascular zone, SCP, and deep capillary plexus foveal vascular density (P < 0.005). Subjects with SCP foveal vascular density >30% or foveal avascular zone <0.1 mm2 had fovea plana. The best-corrected visual acuity of the plana group had no correlation with OCTA quantitative parameters (Pearson |r|<0.18, Spearman |r|<0.44). CONCLUSION: Optical coherence tomography angiography has a high accuracy in diagnosing fovea plana, as its characteristics differ significantly from the normal population. The lack of correlation between the best-corrected visual acuity and OCTA parameters implies that reduced the best-corrected visual acuity is likely to result from coexistent diseases rather than from the foveal structure.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IMAGING OF A CONGENITAL SIMPLE HAMARTOMA OF THE RETINAL PIGMENT EPITHELIUM.

PURPOSE: To report the case of a small pigmented tumor in the macular region investigated using optical coherence tomography angiography (OCT-A) in the context of a multimodal approach. METHODS: Case report. RESULTS: A 24-year-old man was referred for evaluation of an asymptomatic unilateral round comma-shaped pigmented tumor located in the macular region of his right eye. Spectral-domain OCT revealed an irregular hyperreflective mass within the retina, with a thickened hyaloid membrane and abrupt margins, and a complete posterior shadowing effect. On fluorescein angiography, early hyperfluorescence without leakage in the middle and late phases and a subtle halo of hyperfluorescence in the late phase were observed. OCT-A revealed the presence of intrinsic vascularization at the level of the inner capillary plexus, with signal intensity present at the level of the outer capillary plexus. In the superficial scans, the retinal vessels were oriented radially to the lesion and were in continuity with the vascular network within the tumor mass. No choroidal vessels could be identified. CONCLUSION: We report the case of a congenital simple hamartoma of the retinal pigment epithelium investigated using OCT-A as part of multimodal imaging. OCT-A provided a new insight in the assessment of the lesion, differential diagnosis, and follow-up of the patient. This imaging modality could be an important non-invasive tool in the management of congenital hamartomas of the retinal pigment epithelium.

A Prospective Analysis of iStent Inject Microstent Implantation: Surgical Outcomes, Endothelial Cell Density, and Device Position at 12 Months.

PRECIS: The surgical outcome of iStent inject devices is associated with device protrusion within the anterior chamber. Schlemm canal (SC) dilatation has a prognostic value. iStent inject devices do not move within the first year after implantation. INTRODUCTION: The iStent inject is a device designed to be implanted ab-interno through the trabecular meshwork. The present study follows up on our preliminary report, using successive in vivo anterior segment optical coherence tomography (AS-OCT) imaging to analyze the associations between stent positioning, iridocorneal angle structures, and surgical outcomes. METHODS: In total, 54 eyes of 42 patients (73.3±7.4 y) with cataract and mild-to-moderate open-angle glaucoma were examined in this prospective study. All patients underwent implantation of 2 iStent inject devices combined with phacoemulsification. Patients were followed up over a 12-month period. AS-OCT was performed after 3 and 12 months. Thirty unoperated fellow eyes served as control eyes. RESULTS: Intraocular pressure (IOP) decreased from 16.5±4.2 mm Hg at baseline to 15.1±3.7 mm Hg at 12 months (-8.7%; P=0.004), while medications decreased from 1.8±1.0 to 0.5±0.9 (-72.2%; P<0.001). Unmedicated IOP≤18 mm Hg was achieved in 58.8% of operated eyes. No sight-threatening complications were reported. On AS-OCT, 44.9% of devices were buried within the trabeculum. Device position was unchanged between scans. Regression analysis elicited significant predictors: SC dilatation effect [risk ratio (RR)=0.230; P=0.003], greatest SC diameter (RR=0.991; P=0.049), extrusion of the most anterior device (RR=0.993; P=0.012), gonioscopically visible devices (RR=0.406; P=0.040), baseline treatments (RR=2.214; P=0.001), and baseline IOP (RR=0.184; P=0.006). Endothelial cell density decreased by 14.6% at 12 months (P<0.001). CONCLUSIONS: This study demonstrates the IOP-lowering and medication-lowering potential of iStent inject surgery in primary open-angle and pseudoexfoliative glaucoma. It confirms that surgical outcomes are positively associated with device protrusion within the anterior chamber, and suggests SC dilatation effect as a favorable prognostic indicator. It shows that stents are stable in time, highlighting the importance of the initial implantation location.

MULTIPLE SEROUS PIGMENT EPITHELIAL DETACHMENTS IN ASSOCIATION WITH MAJOR WEIGHT LOSS: CASE REPORT AND REVIEW OF THE LITERATURE.

PURPOSE: To report about two cases with bilateral multiple serous pigment epithelial detachments (sPED) following major acute weight loss. METHODS: Retrospective chart review of patients who presented with bilateral multiple sPED following acute major weight loss. The files were reviewed for their general and ophthalmic history, medication, ophthalmic status, optical coherence tomography (OCT) and enhanced depth imaging, fluorescein and indocyanine green angiography, arterial pressure, and laboratory workup. RESULTS: Two patients, both women, aged 45 and 50 years were identified. The sPED counted 50 and 5, respectively. They were located in the mid-periphery and the macula. Multimodal imaging including optical coherence tomography, fundus autofluorescence, fluorescein angiography, and indocyanine green angiography did not reveal an underlying ocular pathology. However, both patients had a thick choroid (455 µm and 542 µm). They both had gone through intentional major weight loss induced by protein-rich Dukan's diet (-20 kg in 3 months) and gastric bypass with protein-enriched diet (-35 kg in less than 1 year), respectively. They were substituted with vitamins (vitamin B, C, D). CONCLUSION: Bilateral multiple serous PEDs may occur in the context of acute major weight loss and protein-rich diet. The precise pathogenesis remains to be elucidated. However, potential candidates include the protein-, mineral- and/or vitamin-related metabolism disturbing the pigment epithelium function. A predisposition for a central serous chorioretinopathy like response might have contributed.