Evaluating optical coherence tomography (OCT) findings as potential biomarkers in central nervous system (CNS) lymphoma with or without ocular involvement

Background To evaluate spectral domain optical coherence tomography (SD-OCT) findings as biomarkers in primary central nervous system lymphoma (PCNSL) with or without ocular involvement. Methods This study was a cross-sectional study and patients with a confirmed diagnosis of PCNSL with or without ocular involvement were included. Patient cohort finder tool was used to identify patients with lymphoma using ICD-10 codes (C82–C88), from January 2004 to October 2017. A total of 14,820 patients were identified. Procedure code (92134) for optical coherence tomography (OCT) was then applied to identify patients who had underdone OCT imaging at ophthalmology clinic. Clinic charts of 460 patients with lymphoma and available OCT were reviewed to identify patients with confirmed diagnosis of PCNSL and divided into two groups (Group 1: with and Group 2: without ocular involvement). OCT scans of patients in both study groups were analyzed for the presence of (1) Hyperreflective deposits in choroid, retinal pigment epithelium (RPE), outer and inner retina; (2) RPE thickening; (3) Vitreous debris; (4) Intraretinal fluid; (5) Ellipsoid zone disruption by masked graders. Chi-square was used to analyze the difference between the groups. Results Twenty-two eyes (11 patients) with PCNSL were included this study (Group 1: 6 eyes and Group 2: 16 eyes). Mean age of subjects was 65 years. Five patients (45.45%) were female. There was no statistically significant difference between the groups for the presence of hyperreflective deposits in choroid, RPE, outer and inner retina, and presence of RPE thickening, intraretinal fluid, and ellipsoid zone disruption. Vitreous debris was found more commonly in group 1 subjects (83%) than group 2 (31.25%) (p = 0.029). All subjects in both groups showed hyperreflective deposits in the RPE demonstrating RPE infiltration. However, RPE thickening was noted only in 3 patients (Group1: 1 and Group2: 2). Conclusions OCT finding of hyperreflective deposits present in eyes with lymphoma secondary to PCNSL are also observed in eyes with PCNSL without ocular disease. However, the vitreous deposits are more commonly found in eyes with ocular disease. These hyperreflective deposits can serve as biomarkers for early detection of ocular involvement by PCNSL.

Intravitreal 0.19 mg Fluocinolone Acetonide Implant in Non-Infectious Uveitis

The efficacy of the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN) in the treatment of non-infectious uveitic macular edema (UME) was assessed on twenty-six patients (34 eyes) with non-infectious UME between 2013 and 2020, in a mean follow-up of 18 ± 19.3 (mean ± SD) months. Macular edema was resolved in 24 (70.6%) cases. Five of these eyes had a relapse after 23.2 ± 14 months. Three FAc reinjections were performed and a drying of the macula was observed. After FAc implantation, 24 eyes (70.6%) were completely dry; central retinal thickness (CRT) decreased in 6 eyes (17.6%), but residual intraretinal fluid was still evident. In 20 eyes (58.5%), visual acuity (VA) improved (from +1 to +5 lines) and remained stable in 9 eyes (26.5%). Thirty eyes (88.2%) were pseudophakic at baseline and four were phakic. Three of these eyes had a cataract prior to therapy and the other developed a cataract 2.5 years after the FAc implant was administered. There was an overall increase in intraocular pressure (IOP; +4.4 ± 3.7 mmHg) and eye drops were required in three eyes. The FAc implant led to long-term improvements in mean CRT and VA, and that the side-effect profile was manageable in a clinical setting in patients with non-infectious UME.

Multimodal imaging of bilateral immunogammopathy maculopathy associated to Waldenström’s macroglobulinemia

Aim: Our aim is to report a case with bilateral Waldenström’s macroglobulinemia (WM) associated maculopathy, assessed with multimodal imaging including swept source optical coherence tomography (SS-OCT) and OCT-Angiography (OCT-A). Methods: Observational case report. Case presentation: A 61-year-old diabetic woman with history of treated WM currently in remission, presented with progressive bilateral visual loss. Best-corrected visual acuity was 20/100 in the right eye (RE) and 20/200 in the left eye (LE). Fundus examination showed bilateral microaneurysms and retinal punctuate hemorrhages and a large macular serous detachment in the LE. There was no retinal ischemia on FA nor macular dye leakage. SS-OCT showed a significant schisis-like intraretinal fluid accumulation in the RE and a large prominent macular detachment with significant subretinal fluid accumulation in the LE. Retinal and choriocapillaris vascular densities were normal on OCT-A. Conclusion: Our case illustrated characteristic multimodal imaging findings in WM associated maculopathy such as schisis-like intraretinal fluid accumulation and angiographically silent serous macular detachment. OCT-A could non-invasively analyze macular vascular densities layer-by-layer, without noticing any vascular anomaly.

Short-Term Outcomes following “Switching” to Monthly Ranibizumab in Neovascular Age-Related Macular Degeneration Showing Insufficient Response to Bimonthly Aflibercept

Background/Objectives. To evaluate the efficacy of switching to monthly ranibizumab in neovascular age-related macular degeneration (nAMD) showing an insufficient response to bimonthly aflibercept. Subjects/Methods. A total of 13 nAMD eyes showing an insufficient treatment response to three successive aflibercept injections were enrolled through a retrospective chart review. After switching, three consecutive monthly intravitreal ranibizumab injections were performed. The main outcome measurements included the best-corrected visual acuity (BCVA), central retinal thickness (CRT), presence of intraretinal fluid (IRF), and subretinal fluid (SRF) using optical coherence tomography (OCT) and were measured every month. Results. CRT and logMAR VA were 349.62 ± 223.51 μm and 0.50 ± 0.23 at the baseline and 274.69 ± 148.77 μm and 0.46 ± 0.24, 311.54 ± 192.90 μm and 0.45 ± 0.20 at 1 month after the first and third ranibizumab injections, respectively. The CRT decrease during three ranibizumab injections was statistically significant (38.08 ± 69.52 μm, p = 0.033 ). Change in VA was not statistically significant. The percentage of eyes with SRF was 100% at baseline and 53.8%, 76.9%, and 69.2% one month after each ranibizumab injections. The percentage of eyes with IRF was 38.5% at baseline and 23.1%, 23.1%, and 15.4%, respectively, after switching. Conclusion. Switching to monthly ranibizumab in nAMD showing an insufficient response to bimonthly aflibercept led to immediate anatomical improvement. It can be considered in countries where the healthcare insurance system limits the minimum injection interval of aflibercept.

A comparative study of type 1 neovascularization: Neovascular age-related macular degeneration versus pachychoroid neovasculopathy

Purpose: This study aimed to compare type 1 choroidal neovascularization (CNV) characteristics in eyes with pachychoroid neovasculopathy (PNV) and neovascular age-related macular degeneration (nAMD) using optical coherence tomography angiography (OCTA). Methods: Treatment naive 23 eyes of 23 patients with PNV and 24 eyes of 24 patients with nAMD were evaluated. The height of pigment epithelial detachment (PED) and the central macular thickness were determined. OCTA sensitivity, CNV area, morphological patterns, and retinal superficial capillary plexus vessel density (SCP-VD) values were compared. The frequency of quiescent CNV, subretinal hyperreflective exudation (SHE), subretinal/intraretinal fluid, serous PED, double-layer sign (DLS), and pachyvessels were noted. Results: CNV was detected on OCTA in 83.3% of nAMD eyes and 91.3% of PNV eyes ( p = 0.66). Indistinct pattern was more common (74% vs 50%) and the CNV area (mm2) was smaller in PNV (0.77 ± 0.54 vs 1.57 ± 1.43) but did not reach significant levels ( p = 0.27 and 0.33 respectively). SCP-VD was similar between the groups ( p = 0.38). Statistically significant differences were found between groups in age and subfoveal choroidal thickness ( p < 0.05). DLS and pachyvessels were found to be more frequently in PNV ( p < 0.05). However, both groups had similar rates of quiescent CNV, SHE, subretinal/intraretinal fluid, and serous PED ( p > 0.05). Conclusion: Morphological features, area, and activation findings of type 1 CNV may play a limited role in differentiating nAMD and PNV cases.

Intraretinal, sub-retinal, and sub-retinal pigmented epithelium fluid in non-exudative age-related macular degeneration: follow-up with OCT imaging

Background/objectives: To evaluate the presence and evolution of fluid in non-exudative age-related macular degeneration (AMD) through serial OCT. Subjects/methods: A retrospective analysis of eyes with non-exudative AMD with a minimum of 4 year follow-up was done. Parameters including intraretinal fluid (IRF), subretinal fluid (SRF), and sub-retinal pigment epithelium (RPE) fluid (SRPEF); subfoveal choroidal thickness (SFCT) and type of drusen were evaluated using optical coherence tomography (OCT) scans at baseline and follow up visits. Results: Seventy-two eyes (in 63 patients) were followed up for an average of 5.83 ± 2.17 years. A total of 26/72 (36%) and 29/65 (52%) of the non-exudative eyes had fluid during baseline and the last visit. Seven eyes (10%) out of 72 eyes converted into exudative AMD or neo-vascular AMD (nAMD) during the study period. SRPEF at baseline was most common fluid location for non-exudative eyes that eventually converted to nAMD. Conclusion: Non-exudative fluid including IRF, SRF, and SRPEF is seen in patients with non-exudative AMD with increasing incidence during long term follow-up.

Efficacy and safety of brolucizumab versus aflibercept in eyes with polypoidal choroidal vasculopathy in Japanese participants of HAWK

PurposeTo compare the efficacy and safety of brolucizumab versus aflibercept in eyes with polypoidal choroidal vasculopathy (PCV) over 96 weeks in the HAWK study.DesignHAWK was a global, 2-year, randomised, double-masked, multicentre phase III trial in participants with neovascular age-related macular degeneration.MethodsOf the Japanese participants with PCV, 39 received brolucizumab 6 mg and 30 received aflibercept 2 mg. After 3 monthly loading doses, brolucizumab-treated eyes received an injection every 12 weeks (q12w) but were adjusted to q8w if disease activity was detected. Aflibercept-treated eyes received fixed q8w dosing. Mean change in best-corrected visual acuity (BCVA), the proportion of participants on q12w, retinal thickness, retinal fluid changes and safety were assessed to Week 96.ResultsMean change in BCVA (early treatment diabetic retinopathy study (ETDRS) letters) from baseline to week 48/week 96 was+10.4/+11.4 for brolucizumab and +11.6/+11.1 for aflibercept. For brolucizumab-treated eyes, the probability of only q12w dosing after loading through week 48 was 76%, and 68% through week 96. Fluid resolution was greater with brolucizumab than aflibercept: respective proportions of eyes with intraretinal fluid and/or subretinal fluid were 7.7% and 30% at week 48% and 12.8% and 16.7% at week 96. Brolucizumab exhibited an overall well-tolerated safety profile despite a higher rate of intraocular inflammation compared with aflibercept.ConclusionIn Japanese eyes with PCV, brolucizumab q12w/q8w monotherapy resulted in robust and consistent BCVA gains that were comparable to q8w aflibercept dosing. Anatomical outcomes favoured brolucizumab over aflibercept, with 76% of brolucizumab participants maintained on q12w dosing after loading to week 48.

Analysis of antiangiogenic therapy in Retinal Angiomatous Proliferation

Retinal angiomatous proliferation (RAP) is a separate form of neovascular age-related macular degeneration (nAMD), which accounts for 12-15% of newly diagnosed patients with nAMD [14]. It is believed that the development of RAP is associated with vascular endothelial growth factor (VEGF) [12]. Purpose. The main goal of our work was to conduct a retrospective analysis of the use of anti-VEGF therapy in patients with retinal angiomatous proliferation. Material and methods. Under observation in 14 patients (14 eyes) with retinal angiomatous proliferation. The age of the patients ranged from 52 to 80 years. The observation period was 4 years. OCT data were used to assess the presence / absence of neuroepithelial detachment, the presence / absence of retinal pigment epithelium detachment and the presence / absence of intraretinal fluid, and the incidence of RP rupture was assessed. Results. The maximally corrected visual acuity increased already in the first year of follow-up compared to BCVA before treatment, under the condition of intravitreal injections (IVI) of anti-VEGF drug aflibercept, and continued to remain at the same level throughout the observation period. In most patients, subretinal fluid was resorbed as early as 1 year of follow-up against the background of antiangiogenic therapy; by 3 years of follow-up, ONE remained only in 2 patients. Before treatment, 71.4% of patients had intraretinal fluid (IRF) in the macular zone according to OCT data; by the 3rd year of follow-up, the percentage of patients with IRF was 33.3%. Conclusion. In the course of this work, we have shown a positive effect of intravitreal administration of the anti-VEGF drug aflibercept in patients with retinal angiomatous proliferation. Key words: age-related macular degeneration, retinal angiomatous proliferation, anti- VEGF, macular edema.

Approaches to antiangiogenic therapy for aneurysmal type 1 neovascularization

Purpose. To study the primary response to anti-VEGF therapy with Aflibercept in patients with aneurysmal type 1 neovascularization (AN type 1). Material and methods. 11 patients with type I AN were examined. All patients underwent a standard ophthalmological examination and additionally underwent: determination of the maximum corrected visual acuity according with ETDRS (Early Treatment Diabetic Retinopathy Study) charts, OCT, OCT-angiography and indocyanine-green angiography to clarify the diagnosis. Results. According to the results of the study, against the background of three loading injections, there is a significant decrease in the height of RPE detachment (p=0.029), an unreliable decrease in the central retinal thickness (p=0.088) due to resorption of sub- and intraretinal fluid, and an increase in BCVA (p=0.285), due to compliance with the regime. At the 12th month of the study, there was an increase in the central thickness of the retina and the height of RPE detachment. The achieved results were not preserved, which can be explained by compliance with loading doses and further non-compliance with the interval between injection. On average, 6.5 IVIs were performed per year. Conclusions. Against the background of anti-VEGF therapy with aflibercept in patients with type I aneurysmal neovascularization, a positive effect of treatment is observed. But it is necessary to carry out regular monitoring and treatment to maintain the achieved results. Key words: polypoidal choroidal vasculopathy, aflibercept, anti-VEGF, retinal epithelium pigment detachment, aneurysmal neovascularization.