Toward a Specific Classification of Polypoidal Choroidal Vasculopathy: Idiopathic Disease or Subtype of Age-Related Macular Degeneration

PURPOSE To suggest a clinical distinction between idiopathic polypoidal choroidal vasculopathy (PCV) and secondary polyps associated with neovascular age-related macular degeneration (NV-AMD). METHODS The study was a retrospective case series of 52 eyes of 52 consecutive patients (31 females and 21 males) diagnosed with PCV. Initial diagnosis was based on scanning laser ophthalmoscope-indocyanine green angiography (SLO-ICGA) in association with fluorescein angiography (FA) and optical coherence tomography (OCT). All the data and images were analyzed in a masked fashion by four experienced examiners in two different sessions: the first, to classify patients into the two hypothesized groups (idiopathic polyps or NV-AMD-related polyps); the second, following a predetermined scheme, to describe objective features. The results obtained in each session underwent a cross multivariate analysis to identify statistically significant differences (P ≤ 0.05) between the two groups. RESULTS The two groups were clinically different on the basis of FA (leakage origin [P = 0.001] and presence of drusen [P = 0.001]), ICGA (evidence of choroidal neovascularization [CNV; P = 0.001] and/or branching vascular network [BVN; P = 0.001]), OCT imaging (type of pigmented epithelium detachment [P = 0.001], presence of BVN [P = 0.001], and subfoveal choroidal thickness [P = 0.001]). Further significant differences were observed according to the location of lesion (uni- or multifocal) (P = 0.001), type of CNV (P = 0.001), and best-corrected visual acuity (P = 0.001). CONCLUSIONS Our study demonstrated clinical and statistically significant differences between idiopathic PCV and NV-AMD-related polyps that could be considered as distinct entities. Although they share some similarities, mainly the sub-RPE location, the ability to identify a specific clinical pattern suggests a more specific therapeutic approach for these two entities

The Therapeutic Effects of Bevacizumab in Patients with Polypoidal Choroidal Vasculopathy

A proper description of the biosynthesis of fungal β-lactam antibiotics requires detailed knowledge of the cell biology of the producing organisms. This involves a delineation of the compartmentalization of the biosynthetic pathways, and of the consequential transport steps across the cell-boundary plasma membrane and across organellar membranes. Of the enzymes of the penicillin biosynthetic pathway in Penicillium chrysogenum and Aspergillus nidulans, δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) and isopenicillin N synthase (IPNS) probably have a cytosolic location. Acyl-coenzyme A:isopenicillin N acyltransferase (IAT) is located in microbodies. Of the two enzymes that may be involved in activation of the side chain, acetyl-coenzyme A synthetase (ACS) is located in the cytosol, and phenylacetyl-coenzyme A ligase (PCL) is probably located in the microbody. All enzymes of the cephalosporin biosynthesis pathway in Cephalosporium acremonium probably have a cytosolic location. The vacuole may play an ancillary role in the supply of precursor amino acids, and in the storage of intermediates. The distribution of precursors, intermediates, end- and side-products, the transport of nutrients, precursors, intermediates and products across the plasma membrane, and the transport of small solutes across organellar membranes, is discussed. The relevance of compartmentalization is considered against the background of recent biotechnological innovations of fungal β-lactam biosynthesis pathways.

Impact of Polyp Regression on 2-year Outcomes of Intravitreal Aflibercept Injections: A Treat-and-Extend Regimen for Polypoidal Choroidal Vasculopathy

We conducted intravitreal aflibercept injections (IVAs) for 37 Japanese patients (28 males, 9 females, mean age 73.4 years) with polypoidal choroidal vasculopathy (PCV), with a treat-and-extend regimen (TER). We evaluated the impact of polyp regression after a loading dose (2-mg IVA 1×/month for 3 months) on the patients' 2-year treatment outcomes. Thirty-seven eyes were treated with IVA by a TER for 2 years. We divided the patients into 2 groups based on their polyp status after the loading dose: polyp regression (PR+) (n=19) and no polyp regression (PR−) (n=18). We compared the groups’ best-corrected visual acuity (BCVA), central retinal thickness (CRT), recurrence rate, total number of injections, and final treatment interval. Both the BCVA and CRT were significantly improved by the treatment in both groups, with no between-group difference in the amount of change (p=0.769). In the polyp regression (+) group, recurrence was significantly less common (p=0.03), the mean total number of injections was significantly lower (p=0.013), and the mean treatment interval was significantly longer (0.042). Regarding the 2-year outcomes for PCV, the eyes with post-loading-dose polyp regression demonstrated less frequent recurrence and required fewer numbers of injections compared to the eyes without polyp regression

Twenty‐four‐month real‐life treatment outcomes of polypoidal choroidal vasculopathy versus type 1 macular neovascularization in Caucasians

Background To compare 24‐month real‐world outcomes of Vascular Endothelial Growth Factor (VEGF) inhibitors for Polypoidal Choroidal Vasculopathy (PCV) and type 1 Macular Neovascularization (MNV) in a Caucasian population.MethodsRetrospective analysis from a prospectively designed observational database. Data from Italian centres participating in the Fight Retinal Blindness! (FRB!) project were collected. Treatment‐naïve PCV or type 1 MNV commencing treatment after January 2009 were included. The primary outcome was 24‐month visual acuity (VA) change; other outcomes included baseline characteristics, number of anti‐VEGF injections, time to lesion inactivation and proportion of active visits.ResultsA total of 322 eyes (114 PCVs) from 291 patients were included. Median [Q1, Q3] VA at baseline was comparable (70 [55, 75.8] vs. 70 [58.8, 75] letters, p = 0.95). Adjusted VA change at 2 years was higher in PCV (mean [95% CI], +1.2 [−1.6, 4.1] vs. −3.6 [−6, −1.2] letters, p = 0.005). PCV received fewer anti‐VEGF injections over the first 24 months of treatment than type 1 MNV (median [Q1, Q3], 8 [5, 10] vs. 9 [7, 12.2] injections, p = 0.001), inactivated earlier (median [Q1, Q3], 235 [184, 308] vs. 252 [169, 343] days, p = 0.04) and was less frequently graded ‘active’ (62% vs. 68% of visits, p = 0.001). Conclusions PCV had slightly better VA outcomes over 24 months of treatment than type 1 MNV after receiving less anti‐VEGF injections. These results suggest a possible overlap of the two clinical entities with similar visual prognosis in Caucasians

Central serous chorioretinopathy: Recent findings and new physiopathology hypothesis.

Central serous chorioretinopathy (CSCR) is a major cause of vision threat among middle-aged male individuals. Multimodal imaging led to the description of a wide range of CSCR manifestations, and highlighted the contribution of the choroid and pigment epithelium in CSCR pathogenesis. However, the exact molecular mechanisms of CSCR have remained uncertain. The aim of this review is to recapitulate the clinical understanding of CSCR, with an emphasis on the most recent findings on epidemiology, risk factors, clinical and imaging diagnosis, and treatments options. It also gives an overview of the novel mineralocorticoid pathway hypothesis, from animal data to clinical evidences of the biological efficacy of oral mineralocorticoid antagonists in acute and chronic CSCR patients. In rodents, activation of the mineralocorticoid pathway in ocular cells either by intravitreous injection of its specific ligand, aldosterone, or by over-expression of the receptor specifically in the vascular endothelium, induced ocular phenotypes carrying many features of acute CSCR. Molecular mechanisms include expression of the calcium-dependent potassium channel (KCa2.3) in the endothelium of choroidal vessels, inducing subsequent vasodilation. Inappropriate or over-activation of the mineralocorticoid receptor in ocular cells and other tissues (such as brain, vessels) could link CSCR with the known co-morbidities observed in CSCR patients, including hypertension, coronary disease and psychological stress

Evaluation of Abicipar Pegol (an Anti-VEGF DARPin Therapeutic) in Patients With Neovascular Age-Related Macular Degeneration: Studies in Japan and the United States

BACKGROUND AND OBJECTIVE: To evaluate comparability of abicipar pegol (abicipar) effects in patients with treatment-naïve neovascular age-related macular degeneration (nAMD) in Japan and the United States. PATIENTS AND METHODS: Phase 2, multicenter, randomized, double-masked, 20-week studies (BAMBOO, Japan; CYPRESS, United States). Patients (n = 25 each study) received three monthly intravitreal injections of abicipar 1 mg or 2 mg or five monthly intravitreal injections of ranibizumab 0.5 mg. RESULTS: Mean best-corrected visual acuity change from baseline at week 16 (primary endpoint) for abicipar 1 mg, abicipar 2 mg, and ranibizumab was +7.8 letters, +8.9 letters, and +17.4 letters (BAMBOO); +4.4 letters, +10.1 letters, and +15.2 letters (CYPRESS). Mean central retinal thickness change from baseline was −187.3 μm, −196.5 μm, and −230.4 μm (BAMBOO); −106.5 μm, −112.8 μm, and −124.4 μm (CYPRESS). Uveitis or vitritis was reported in three abicipar-treated patients. CONCLUSION: Abicipar demonstrated extended duration of effect and safety that were comparable between Japanese and non-Japanese patients with nAMD. Abicipar effectively treated Japanese patients with polypoidal choroidal vasculopathy

Incidence, risk factors and outcomes of submacular haemorrhage with loss of vision in neovascular age-related macular degeneration in daily clinical practice: data from the FRB! registry

PURPOSE The main purpose of the study was to report the estimated incidence, cumulative rate, risk factors and outcomes of submacular haemorrhage (SMH) with loss of vision in neovascular age-related macular degeneration (nAMD) receiving intravitreal injections (IVT) of vascular endothelial growth factor (VEGF) inhibitor in routine clinical practice. METHODS Retrospective analysis of treatment-naïve eyes receiving IVTs of VEGF inhibitors (ranibizumab, aflibercept or bevacizumab) for nAMD from 1 January 2010 to 31 December 2020 that were tracked the Fight Retinal Blindness! registry. Estimated incidence, cumulative rate and hazard ratios (HR) of SMH with loss of vision during treatment were measured using the Poisson regression, Kaplan-Meier survival curves and Cox proportional hazard models. RESULTS We identified 7642 eyes (6425 patients) with a total of 135 095 IVT over a 10-year period. One hundred five eyes developed SMH with loss of vision with a rate of 1 per 1283 injections (0.08% 95% confidence interval [95% CI] [0.06; 0.09]). The estimated incidence [95% CI] was 4.6 [3.8; 5.7] SMH with loss of vision per year per 1000 treated patients during the study. The cumulative [95% CI] rate of SMH per patient did not increase significantly with each successive injection (p = 0.947). SMH cases had a mean VA drop of around 6 lines at diagnosis, which then improved moderately to a 4-line loss at 1 year. CONCLUSIONS Submacular haemorrhage (SMH) with loss of vision is an uncommon complication that can occur at any time in eyes treated for nAMD in routine clinical practice, with only limited recovery of vision 1 year later

One-year real-world outcomes of ranibizumab 0.5 mg treatment in Taiwanese patients with polypoidal choroidal vasculopathy: a subgroup analysis of the REAL study

AIM: To assess the effectiveness and safety of ranibizumab 0.5 mg in Taiwanese patients with polypoidal choroidal vasculopathy (PCV) by performing a retrospective exploratory subgroup analysis of the REAL study. METHODS: REAL was a 12-month, observational, prospective, non-interventional phase IV post-marketing surveillance study conducted at 9 centers in Taiwan. The study collected data as part of the routine patient visits from the medical records of patients with neovascular age-related macular degeneration treated with ranibizumab 0.5 mg according to local standard medical practice and local label and/or reimbursement guidelines. The presence of PCV at baseline was determined using indocyanine green angiography. RESULTS: At baseline, PCV was diagnosed in 64 of the 303 enrolled patients (21.1%). Of these, 41 patients (64.1%) had received prior treatment; 15 (23.4%) patients had received ranibizumab. The intent-to-treat population included 58 patients; 47 (80%) who received ranibizumab and 11 (20%) who received ranibizumab plus photodynamic therapy (PDT; 9 patients received once, 2 patients received twice). Bevacizumab was used as a concomitant medication in a similar percentage of patients who received ranibizumab (43%, n=20) or ranibizumab plus PDT (45%, n=5). In patients who received ranibizumab, visual acuity (VA) at baseline was 50.1±12.9 Early Treatment Diabetic Retinopathy Study letters, and the gain at month 12 was 1.1±17.8 letters. In patients who received ranibizumab plus PDT, VA at baseline was 51.4±15.9 letters, and there was a marked gain in VA at month 12 (14.0±9.2 letters, P=0.0009). In the intent-to-treat population, the reduction in central retinal subfield thickness from baseline at month 12 was 69.6±122.6 µm (baseline: 310.8±109.8 µm, P=0.0004). The safety results were consistent with the well-characterized safety profile of ranibizumab. CONCLUSION: In real-world settings, ranibizumab 0.5 mg treatment for 12mo results in maintenance of VA and reduction in central retinal subfield thickness in Taiwanese patients with PCV. Improvements in VA are observed in patients who received ranibizumab plus PDT. There are no new safety findings

Peripapillary Choroidal Thickness Change of Polypoidal Choroidal Vasculopathy after Anti-vascular Endothelial Growth Factor

PURPOSE: To investigate the peripapillary choroidal thickness (PCT) of polypoidal choroidal vasculopathy (PCV) and exudative age-related macular degeneration (AMD) and to evaluate their responses to anti-vascular endothelial growth factor (VEGF). METHODS: Thirty eyes with PCV and 25 eyes with exudative AMD who were treatment naïve were included in this study. PCT and subfoveal choroidal thickness were evaluated both before and after intravitreal anti-VEGF. RESULTS: The initial mean PCT of PCV (153.78 ± 56.23 μm) was thicker than that of exudative AMD (88.77 ± 23.11 μm, p < 0.001). Temporal, superior, nasal, and inferior PCTs of PCV were all thicker than those observedin exudative AMD (all p < 0.05). After anti-VEGF, the mean PCT of PCV was significantly reduced (134.17 ± 41.66 μm, p < 0.001), but the same was not true not in exudative AMD (86.87 ± 22.54 μm, p = 0.392). PCTshowed a similar tendency in all quadrants. CONCLUSIONS: PCV exhibits a thick choroid in the peripapillary region. PCT decreases after anti-VEGF in PCV but not in exudative AMD. In exudative AMD, subfoveal choroidal thickness decreased, but that in the peripapillary region did not.ope

Response of neovascular central serous chorioretinopathy to an extended upload of anti-VEGF agents

Purpose To determine the anatomical and functional outcomes of an extended 6-month intravitreal anti-vascular endothelial growth factor (anti-VEGF) upload in choroidal neovascularization (CNV) secondary to chronic central serous chorioretinopathy (CSCR). Methods A retrospective database analysis was performed applying the following inclusion criteria: (1) diagnosis of CSCR, (2) diagnosis of secondary CNV, and (3) treatment of at least six consecutive injections of anti-VEGF. Outcome measures included the change of central retinal subfield thickness, remodeling of the pigment epithelium detachments, and change in visual function. Results Twenty-one eyes of 21 patients were included. Mean patient age was 65 ± 8.3 years, and 35% of the patients (n = 8) were female. Mean disease duration before diagnosis of CNV was 48 ± 25.3 months. Mean central retinal thickness decreased from 346 ± 61 to 257 ± 57 μm (p < 0.01) after the sixth injection while mean visual acuity improved from 0.65 ± 0.35 to 0.49 ± 0.29 (logMAR; p < 0.01). Of note, an extended upload of six as opposed to three injections yielded an additional mean central retinal thickness reduction (280 ± 46 μm vs. 257 ± 57 μm, p = 0.038). Significant CNV remodeling was observed as a decrease in pigment epithelium detachment (PED) vertical (p = 0.021) and horizontal diameter (p = 0.024) as well as PED height (p < 0.01). Conclusion An extended anti-VEGF upload of six consecutive injections seems to be effective in inducing CNV remodeling and fluid resorption in CNV complicating chronic CSCR