Retinal Pigment Epithelial Detachment Research Articles

Анализ применения антиангиогенной терапии у пациентов с ретинальной ангиоматозной пролиферацией

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.

English

BACKGROUND Optical Coherence Tomography (OCT) is a commonly used non invasive imaging instrument useful for the diagnosis and follow up of macular disorders, but it has its own share of drawbacks in the presence of media opacities like corneal oedema, dense cataract and vitreous haemorrhage. We wanted to study and interpret the various patterns of common macular diseases on optical coherence tomography. METHODS 100 patients having macular diseases with no other ocular pathology were selected by simple random sampling. The patients were studied and followed up from day 1 of OPD during the period from January 2019 to December 2019 in rural hospital at Latur. All patients suspected of any macular disorder by slit lamp bio-microscopy with 78D or 90D examination were subjected to OCT evaluation. RESULTS On observation, out of 100 cases of macular pathology, 44 % (44 patients) with age related macular degeneration(ARMD), diabetic macular oedema ( DME) 36 % (36 patients), central serous retinopathy (CSR) 10 % (10 patients), myopic maculopathy (MM) 7 % (7 patients), macular hole (MH) 3 % (3 patients) were found in our study. In ARMD patients our OCT findings were hard drusens in retinal pigment epithelium (RPE), detachment of neurosensory retina and retinal pigment epithelium whereas in patients of DME our OCT findings were cyst like hyporeflective spaces within the retina, with retinal thinning and loss of foveal depression. In patients of CSR our findings were separation of sensory retina from RP, in myopic maculopathy our OCT findings were presence of macular retinoschisis and in patients of MH our findings were showing attachment of the posterior hyaloids to the fovea, separation of a small portion of the sensory retina from RPE in the foveolar region and intraretinal cystic changes. CONCLUSIONS OCT plays a crucial role when added along with the clinical examination in the diagnosis and interpretation of common macular disorders. KEYWORDS Optical Coherence Tomography, Age Related Macular Degeneration, Macular Hole, Myopic Maculopathy

Macular associations of tilted disc syndrome.

Purpose:The aim of this study was to describe macular changes associated with tilted disc syndrome (TDS) using multimodality imaging.Methods:This is a retrospective observational study of the consecutive TDS cases which were studied for macular changes using color fundus photographs and optical coherence tomography (OCT). Fundus autofluorescence, fundus fluorescein angiography, and OCT angiography were performed wherever required.Results:Twenty consecutive TDS cases (36 eyes) were included. OCT showed inferior depression of all layers in specific scans and macular pathologies seen included lamellar macular hole, full-thickness macular hole, retinal pigment epithelial detachment, acute and resolved subretinal fluid, central serous chorioretinopathy, and choroidal neovascular membrane. Macular involvement was seen in 13 eyes (36.11%) while in the remaining 23 eyes, outer retinal changes were seen on OCT in 9 eyes and normal retinal layers in 14 eyes (38.89%).Conclusion:Various macular pathologies associated with TDS are described using multimodality imaging. These provide understanding of changes which can occur with TDS. It also highlights the need for recognition, differentiation from similar confusing entities, and the necessity to follow-up of these cases carefully to detect the macular changes earlier.

Safety and efficacy of rogaratinib in combination with atezolizumab in cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (UC) and FGFR mRNA overexpression in the phase Ib/II FORT-2 study.

4521 Background: Rogaratinib (R) is a novel pan-FGFR inhibitor that showed promising efficacy and safety in a Phase I trial in pts with advanced solid tumors, including UC, with FGFR1-3 mRNA overexpression. The Phase Ib/II FORT-2 study (NCT03473756) of R plus atezolizumab (A) in pts with first-line cisplatin-ineligible, FGFR-positive, advanced/metastatic UC previously identified a maximum tolerated dose of R 600 mg twice daily (BID) plus A (1200 mg every 3 weeks) . We report updated safety, efficacy, and the recommended Phase II dose (RP2D) for combination therapy from the Phase Ib study. Methods: Pts with cisplatin-ineligible, locally advanced/metastatic UC with FGFR1/3 mRNA overexpression detected by RNA in situ hybridization of archival tissue (RNAscope) received oral R 600 mg BID plus A 1200 mg on day 1 of a 21-day cycle. Archival tissue was examined for programmed cell-death ligand 1 (PD-L1) protein expression levels, FGFR3-activating mutations via a targeted Illumina NGS panel, and FGFR fusions via an Archer fusion plex assay. Primary objectives were safety, tolerability, and determination of the RP2D. Results: 26 pts (enrolled May 25, 2018 to Nov 25, 2020) were treated; 89% were male, median age was 76 years (range 47-85), 58% had an ECOG performance status of 1, and 77% displayed low or absent (negative or non-detectable) PD-L1 expression (combined positive score < 10%). Common treatment-emergent adverse events (TEAEs) included diarrhea (n = 17, 65%; 1 grade [G] 3), hyperphosphatemia (n = 15, 58%; all G1 or 2), and nausea (n = 11, 42%; 1 G3). The most common G3/4 TEAEs were elevated lipase without pancreatitis (n = 5, 19%), elevated amylase (n = 3, 12%), and rash and syncope (n = 2, 8% each). TEAEs led to interruption/reduction/discontinuation of R in 69%/46%/19% of pts. R-related unique TEAEs were hyperphosphatemia in 15 pts (58%) and retinal pigment epithelium detachment in 1 pt (4%). G5 events occurred in 3 pts (12%), unrelated to treatment. 13 of 24 evaluable pts (54%) had an objective response (OR) per RECIST v1.1. The disease control rate was 83%, including 3 pts (13%) with a complete response (CR), 10 (42%) with a partial response (PR), and 7 (29%) with stable disease. Median duration of response was not reached. OR rate was 56% (2 CRs and 7 PRs) in the 16 pts with tumors having low/negative PD-L1 protein and FGFR3 mRNA overexpression without mutation. The RP2D for R+A was 600 mg BID. Conclusions: First-line treatment with the RP2D of R+A achieved favorable clinical efficacy and tolerability in pts with cisplatin-ineligible, metastatic UC characterized by high FGFR1/3 mRNA expression and generally low/negative PD-L1 expression. Encouraging efficacy was observed regardless of PD-L1 expression or FGFR3 mutation status, warranting future investigation. Clinical trial information: NCT03473756.

Differentiating Exudative Macular Degeneration and Polypoidal Choroidal Vasculopathy Using OCT B-Scan

Although polypoidal choroidal vasculopathy (PCV) is best diagnosed with indocyanine green angiography (ICGA), ICGA is often unavailable or not ordered. OCT is widely available, and OCT B-scan can visualize polypoidal lesions diagnostic of PCV as inverted U-shaped elevations of the retinal pigment epithelium (RPE) with heterogeneous reflectivity and sometimes ring-shaped lesions within the polypoidal lesion. This study aims to differentiate findings between eyes diagnosed with PCV or typical exudative age-related macular degeneration (AMD) using ICGA and then compares findings noted on the OCT B-scan line scan in each group. Retrospective, chart review. Clinical features of eyes with PCV and typical exudative AMD were compared by using ICGA. Eyes with PCV were evaluated for inverted U-shaped polypoidal lesions, which are the main differentiating finding of PCV from typical exudative AMD. Data collected included presence of subretinal fluid (SRF), macular edema or intraretinal edema, subretinal hyperreflective material (SHRM), and retinal pigment epithelial detachment (RPED). These findings were evaluated in 2 parts: baseline and after 6 to 9 months of antiangiogenic therapy. Additionally, analysis was performed for the presence of polypoidal lesions before and after treatment. Presence of inverted U-shaped lesions on OCT B-scan following treatment. A total of 112 eyes of 106 patients were included. A total of 69 eyes were diagnosed with PCV, and 43 eyes were diagnosed with typical exudative AMD. Compared with AMD eyes, PCV eyes had an increased prevalence of SRF at baseline and after 6 to 9 months of treatment, but the prevalence of macular edema, SHRM, and RPED was similar at baseline and at 6 to 9 months after treatment. In PCV eyes, the presence of visible polypoidal lesions decreased from 56.5% to 24.6% after treatment. If PCV is suspected in an anti-vascular endothelial growth factor (VEGF)-resistant case of exudative AMD, in the absence of ICGA availability, it is important to look at the baseline OCT B-scan before therapy for evidence of polypoidal lesions. The characteristic inverted U-shaped elevation was present in more than half of PCV eyes on OCT B-scan at baseline but disappeared after antiangiogenic therapy in 56.4% of cases in which this was initially identified. Subretinal fluid was more prevalent in PCV eyes than non-PCV AMD eyes.

Dietary flavonoids are associated with longitudinal treatment outcomes in neovascular age-related macular degeneration.

To assess whether dietary intake of flavonoids are associated with longitudinal treatment outcomes of patients with neovascular age-related macular degeneration (nAMD). 547 participants with nAMD were recruited at baseline, 494 were followed-up after receiving 12 months of anti-vascular endothelial growth factor (anti-VEGF) therapy. Baseline dietary intake of flavonoids was determined using a validated food frequency questionnaire. At follow-up, presence of intra-retinal and sub-retinal fluid (IRF and SRF), retinal pigment epithelium detachment and measurements of central macular thickness (CMT) were recorded from optical coherence tomography scans. Visual acuity (VA) was documented using LogMAR charts. Participants in the first tertile of intake of the flavonol quercetin, and the flavan-3-ols epigallocatechin-3-gallate and epigallocatechin had significantly worse vision than participants in the third tertile-multivariable-adjusted least square (LS) mean VA: 14.68 vs. 19.53 (p = 0.04); 14.06 vs. 18.89 (p = 0.04); 13.86 vs. 18.86 (p = 0.03), respectively. Participants in the first compared to the third tertile of flavan-3-ol, epigallocatechin-3-gallate and epigallocatechin intake all had a twofold higher risk of IRF, multivariable-adjusted p trend of: 0.03, 0.01 and 0.02, respectively. The first vs. the third tertile of tea intake had significantly worse vision (LS mean VA: 13.49 vs. 19.04, p = 0.02), increased risk of IRF (OR 2.13, 95% CI 1.18-3.85) and greater mean CMT (279.59 μm vs. 256.52 μm, p = 0.04). Higher intakes of dietary flavonoids, specifically flavonols and flavan-3-ols, could be associated with better long-term treatment outcomes in nAMD patients receiving anti-VEGF therapy. Confirmation of these associations in interventional studies could result in promising new therapeutic approaches to the treatment of nAMD.

Correction to: Diagnostic Performance of Fundus Autofluorescence for Detecting Polypoidal Choroidal Vasculopathy

The author has informed the editor to correct the legend of figure and word in the article as follow: Incorrect legend of figure in the article: Figure 2. Optical coherence tomography of clinical signs of PCV: (A) steep pigment epithelial detachment (sPED); (B) notched pigment epithelial detachment (nPED); (C) double-layer sign (DLS); and (D) hyporeflective lumen, with retinal pigment epithelial detachment. Correct legend of figure: Figure 2. Optical coherence tomography of clinical signs of PCV: (A) steep pigment epithelial detachment (sPED); (B) double-layer sign (DLS); (C) notched pigment epithelial detachment (nPED); and (D) hyporeflective lumen, with retinal pigment epithelial detachment. Incorrect word in the article: What is already known on this topic? FAF is an invasive investigation aimed for RPE evaluation that is used widely in many retinal diseases. Correct word: What is already known on this topic? FAF is a non-invasive investigation aimed for RPE evaluation that is used widely in many retinal diseases.

Swept-Source OCT Angiographic Characteristics of Treatment-Naïve Nonexudative Macular Neovascularization in AMD Prior to Exudation.

PurposeTo investigate the characteristics of treatment-naïve nonexudative macular neovascularization (MNV) in age-related macular degeneration before the onset of exudation using swept-source optical coherence tomography angiography.MethodsMNV area, choriocapillaris (CC) flow deficits (FDs), vessel area density (VAD), vessel skeleton density (VSD), retinal pigment epithelial detachment (PED) volume, mean choroidal thickness (MCT), and choroid vascularity index (CVI) measurements were assessed at two visits prior to exudation. We compared measurements made at the second visit and the rate of change between visits in eyes with and without exudation. The differences in these parameters between eyes with and without subsequent exudation were summarized with 95% confidence intervals (CIs).ResultsTwenty-one eyes with nonexudative MNV were identified and followed. Nine eyes developed exudation, and 12 eyes did not develop exudation. Differences between these groups of eyes for all parameters tended to be small, and the 95% CIs largely ruled out any substantial differences. Overall, eyes with exudation had 24% smaller VAD, 20% smaller VSD, and 33% smaller PED volume measurements. No noteworthy differences were observed for MNV area, CC FDs, MCT, or CVI measurements.ConclusionsThe onset of exudation was correlated with lesions having less vascularity and smaller PED volume measurements, but measurements of MNV area, CC FDs, MCT, and CVI were not correlated with near-term exudation. Investigations are ongoing to further explore these and other anatomic changes as harbingers of near-term exudation.

Optical Coherence Tomography Findings in Ocular Syphilis Involving the Posterior Segment of the Eye

ABSTRACT Purpose To analyse posterior segment optical coherence tomography (OCT) findings in ocular syphilis. Methods Medical records of 54 patients presenting consecutively with syphilitic uveitis were reviewed. Vitreous, retina and choroid (one eye/patient) were assessed by spectral-domain OCT on presentation (54 eyes) and after treatment (31 eyes). Improvement in signs and associations between presenting signs and final best corrected visual acuity (BCVA) were determined by McNemar’s and Fisher’s exact tests. Results Early inner retinal OCT findings included hyperreflective dots (n = 49, 91%), tongue-like projections (n = 44, 81%) and large rounded spots (n = 41, 76%). Common outer retinal findings included thickening, irregularity, elevations and/or detachment of retinal pigment epithelium (n = 46, 85%), and disruption or loss of the ellipsoid zone (n = 33, 61%). Most outer retinal changes resolved with treatment (p < .05), and common presenting signs were not associated with poor final BCVA (p > .05). Conclusion OCT findings have diagnostic value in ocular syphilis, but do not predict prognosis.

Predicting retinal pigment epithelium remodelling and its functional impact.

To identify predictive factors for RPE tear remodelling and its correlation with functional and morphological outcomes. Retrospective longitudinal study of patients with retinal pigment epithelium (RPE) tears secondary to age-related macular degeneration (AMD). Imaging was performed using spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF). RPE layer integrity in the RPE-denuded area was examined with SD-OCT, and variation in the RPE-denuded homogeneous hypofluorescent area was examined with FAF over time for each case (eye). Patients were divided in two groups, according to the presence (Rem) or absence (No Rem) of evidence of RPE tear remodelling. Data were collected at three different time points: at baseline (at diagnosis of exudative AMD), at RPE tear diagnosis, and at the last available follow-up. Using SD-OCT, the following parameters were evaluated: type of CNV, type of PED and its dimensions, presence of subretinal (SRF) or intraretinal (IRF) fluid, central retinal thickness (CRT), presence and location of hyperreflective dots, and dimension and location of RPE tear. This study included 32 eyes from 31 patients (19 female and 12 male), with RPE tears secondary to AMD. RPE remodelling after tear development was evident in 17 (53.1%) eyes after 7 [1-59] months. Anatomical recovery was associated with a younger age at RPE tear diagnosis (73 ± 7 vs. 81 ± 7 years old, p=0.01), smaller and narrower retinal pigment epithelial detachment (PED) at tear diagnosis (height 369 vs. 602 μm, p=0.02; width 2379 vs. 3378 μm, p=0.04), and the presence of SRF at tear diagnosis (94% vs. 53%, p=0.02). After adjusting for other covariates, a younger age at RPE tear diagnosis maintained significant association with RPE tear remodelling. RPE tear remodelling did not correlate with a better visual outcome at last follow-up (43 ± 22.8 vs. 34 ± 23.8 ETDRS letters, p=0.30). Final VA was directly proportional to VA at tear diagnosis (r= 0.654; p<0.001) and correlated negatively with PED width at tear diagnosis (r = -0.388; p=0.03). RPE remodelling was evident in half of our sample and was associated with a younger age, smaller and narrower PED at RPE tear diagnosis, and presence of SRF also at tear diagnosis. Nevertheless, this structural recovery did not result in a better functional outcome.

Polypoidal Choroidal Vasculopathy in Caucasians: Morphological Findings from Multimodal Retinal Imaging

Purpose: The aim of the study was to characterize the morphological features of polypoidal choroidal vasculopathy (PCV) in a large Caucasian population. Methods: We conducteda multicenter, cross-sectional study of treatment-naïve patients with PCV. Baseline fundus photography, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and indocyanine green angiography (ICGA) were assessed by trained medical graders. Typical PCV features were explored, and retinal thickness (RT) and choroidal thickness (CT) measurements were performed. Results: Seventy-nine eyes of 73 patients (mean age, 72.6 ± 11.9 years) were included. ICGA identified macular polyps in 89.9% of cases. SD-OCT revealed mostly subretinal fluid (93.6%) and a retinal pigment epithelium (RPE) detachment in 91.4%, with sharp protrusion in 67.0% of cases. Polyp-like structures were seen in 74.3% of cases, mostly adherent to an elevated RPE (69.6%). Type 1 neovascularization (NV) was identified in 74.7% of patients, while 16.5% had a mixed NV. The mean macular CT was 220.9 ± 83.2 μm (range, 67.9–403.6). Diffuse and focal pachychoroid were observed in 26.6 and 30.4% of patients, respectively. Soft drusen were reported in 62.0% of cases, but retinal hemorrhage occurred in only 19.0% of cases. Conclusion: The morphological features of PCV in Caucasians are similar to those reported in Asians. Pachychoroid signs were found in nearly half of our cohort. However, the mean age at presentation, high prevalence of soft drusen, and low prevalence of large subretinal hemorrhages make PCV closer to age-related macular degeneration in this ethnic group.

An atypically distributed fleck case with multiple retinal pigment epithelial detachments

A 45-year-old female patient presented with complaints of blurred vision and metamorphopsia with a duration of two months. Visual acuities were 0.1 in the right eye and 1.0 in the left eye. Fundus examination revealed bilateral, subretinal, round and yellow-white flecks with scattered localization in the fovea, macula and peripheral retina. Flecks were mostly concentrated in the macula and midperipheral fundus however were rare in the peripheral fundus. In fluorescein angiography, flecks were stained as well-demarcated hyperfluorescent lesions. In optical coherence tomography, there were hump-shaped lesions which have medium degree internal reflectivity at the level of retinal pigment epithelium along with hyporeflective dome-shaped pigment epithelial detachments. No genetic predisposition was found. As a consequence of these findings, the patient was diagnosed with an atypically distributed fleck case with multiple retinal pigment epithelial detachments

Formación atípica de agujero macular después de terapia Anti-VEGF para la degeneración macular asociada a la edad: ¿coincidencia o consecuencia?

Introduction and objectivesAge-related macular degeneration (AMD) is the primary cause of blindness in developed countries, particularly in older adults. Anti-vascular endothelial growth factor (anti-VEGF) intravitreal injection is the current standard treatment for neovascular form of AMD. Studies reporting macular hole (MH) formation following anti-VEGF treatment are limited, and the exact pathogenesis is still under discussion.With the present study, we aim to analyse the clinical features of eyes developing MH after anti-VEGF therapy for neovascular AMD. Materials and methodsPatients were treated with intravitreal anti-VEGF agents for at least one year and stable for at least six months. Best-corrected visual acuity (BCVA) and optical coherence tomography findings were evaluated. ResultsNineteen eyes of 18 patients were included in this study. Patients had an average age of 77.7 years at first visit and eight were female. The average number of injections before the MH formation was four. MH developed after a mean follow-up of 5.1 months after the last injection. Sixteen eyes had (84.2%) had choroidal neovascular membrane without any abnormal vitreomacular traction. Eleven eyes (57.8%) had retinal pigment epithelium detachment (PED), two (10.5%) had an epiretinal membrane (ERM), and one (5.2%) had retinal pigment epithelium (RPE) tear. The mean first and last BCVA was 1.07 ± 0.48 LogMAR (0.3-1.8) and 1.16 ± 0.38 logMAR (0.4-1.8), respectively. ConclusionsA macular hole can be observed in AMD patients receiving anti-VEGF therapy. Increased fibrovascular scar tissue due to subretinal fluid resolution, neovascular membrane contraction, and the presence of PED, RPE tear, and ERM may contribute to MH formation.

Intra- and Intergrader Agreement for Detection of OCT Angiographic Characteristics Associated With Type 3 Neovascularization.

PurposeTo examine the intra- and intergrader agreement on morphologic characteristics of type 3 neovascularization on optical coherence tomography angiography (OCT-A).MethodsOCT-A images of 22 eyes from 21 patients with a new-onset, treatment-naive type 3 neovascularization were included in this cross-sectional retrospective agreement study. Each image was graded three times by two independent medical retina specialists to assess intra- and intergrader agreement. The graders scored the presence or absence of the following vascular and structural features: intraretinal neovascularization (IRN), subretinal neovascularization, sub-retinal pigment epithelium (RPE) neovascularization (SRPEN), retinal choroidal anastomosis (RCA), intraretinal cysts, subretinal fluid, and pigment epithelial detachment. Agreement was analyzed for each feature using Gwet's AC1, к statistics, and percentage of agreement.ResultsThe best agreement (AC1) was found for intraretinal neovascularization (withingrader1: 0.94; withingrader2: 0.93 and between: 1.00) and intraretinal cysts (withingrader1, 1.00; withingrader2, 0.97 and between, 1.00). The poorest intragrader agreements were observed for SRPEN (withingrader1, 0.54 and withingrader2, 0.36) and RCA (withingrader1, 0.45 and withingrader2, 0.52), and the poorest intergrader agreement was found for SRPEN, RCA, and pigment epithelial detachment (0.18, 0.37, and 0.15, respectively).ConclusionsAlthough the agreement values were high for intraretinal features, considerable grader variability was found for the vascular and structural features in the deeper retina or under the RPE. Clinicians should be careful to base therapeutic decisions on qualitative OCT-A assessment, because even well-trained specialists show a considerable grader variation in their subjective evaluation.Translational RelevanceThe clinical value of OCT-A imaging largely depends on the agreement of subjective evaluations by ophthalmologists.

Effectiveness of anti-VEGF therapy for neovascular age-related macular degeneration in different types of exudative fluid localization

To assess the effectiveness of anti-VEGF therapy in different types of fluids localization in neovascular age-related macular degeneration (AMD). The study included 16 people (16 eyes) with exudative AMD. The study included patients with fibrovascular detachment of the retinal pigment epithelium (RPE), subretinal and intraretinal fluid. The patients were divided into two groups: in the first group, fibrovascular RPE detachment was combined with subretinal fluid (9 eyes); in the second group, fibrovascular RPE detachment was accompanied by both sub- and intraretinal fluid (7 eyes). All patients underwent standard ophthalmological examination, which included visometry, biomicroscopy, and ophthalmoscopy under conditions of drug-induced mydriasis. Additionally, OCT of the macular region and OCT-angiography were performed. Over the entire observation period, the first group of patients received an average of 5.11 intravitreal injections (IVI), the second group - 5.14 IVI. Visual acuity was comparable in both groups at the beginning of the study. Subsequently, the treatment resulted in an increase in visual acuity after 3 months in the first (p=0.066) and second (p=0.043) groups, as well as after 12 months in both groups (p=0.043). In the first group of patients, after 12 months, an increase in RPE detachment was observed (p=0.942), which suggests that the disease activity remains underestimated on OCT when RPE detachment and subretinal fluid are combined. In the first group, complete resorption of subretinal fluid occurred in 2 people. In the second group, resorption of subretinal and intraretinal fluid occurred in 6 people. Regardless of the subtype of fluid, anti-VEGF therapy is an effective method for treating exudative AMD. Intravitreal injections are necessary both in the presence of intra- and/or subretinal fluid, and fluid under RPE. The greatest difficulty is assessment of the fluid under the RPE.

A Histological Study of Atherosclerotic Characteristics in Age-Related Macular Degeneration

This study investigated the pathogenesis of age-related macular degeneration (AMD) using histological methods that are commonly used for atherosclerotic vascular disease (ASVD). 1 normal, 3 early dry AMD, and 1 late dry AMD eyes were obtained from the Lions Eye Bank of Oregon and systematically dissected. They were stained with hematoxylin and eosin, Oil red O, Masson, Elastica van Gieson, Alizarin red, and Prussian blue. Additionally, the normal and late dry AMD eyes were immunostained for a-smooth muscle actin, CD45, and CD68 with Nile red and DAPI. Correlations were found between progression of AMD and lipid accumulation in the deep sclera (+), numbers of drusen between the Bruch’s membrane and retinal pigment epithelium (RPE) (+), amount of collagen in the deep sclera (+), and amount of elastin in the deep sclera (-) (P < 0.1). Geographic atrophy, RPE detachment, abnormal choriocapillaris structure, and decreased choriocapillaris density were observed in the fovea of late AMD. There were no stenosis, plaque, hemorrhage, and calcification. Additionally, late AMD tended to have higher smooth muscle thicknesses of the choroidal vascular walls, lower numbers of T lymphocytes in the choroid, and higher numbers of macrophages near the RPE and in the choroid relative to normal (P < 0.1). Macrophages-derived foam cells were detected near the Bruch’s membrane in late AMD. The results show many histological characteristics of ASVD in AMD, which suggests an association between them. They generally support the vascular model of AMD, but some details still need clarification. Funding: This work is supported by the Beijing Natural Science Foundation (project no. 7154215) and the National Natural Science Foundation of China (project no. 81771347). Declaration of Interests: None to declare. Ethics Approval Statement: The study was approved by the Biological Science and Medical Engineering Ethics Committee of the Beihang University. The identification number this committee gave to my approved research is: BM201900085

Retinal pigment epithelial tear in age-related macular degeneration

Retinal pigment epithelial tear (RPET) occurs in a number of diseases, most often in age-related macular degeneration (AMD). RPET develops in the setting of retinal pigment epithelium (RPE) detachment and represents a violation of the integrity of its monolayer accompanied by the formation of a demarcation line between the RPE atrophy area and RPE folds. Its incidence varies widely. In the earlier studies, diagnosis of RPET was performed using fluorescent angiography or angiography with indocyanine green (ICG-FA). The advent of optical coherence tomography made the detection of RPET easier and more accessible. The mechanism of RPET formation is quite polymorphic and ambiguous. Scientific literature contains descriptions of the occurrence of RPET when using both ranibizumab and aflibercept, and bevacizumab in equal proportions, implying that the drug choice does not affect the occurrence of complications. Continuous monitoring and adherence to anti-VEGF therapy leads to better anatomical and functional results in the long term, which is crucial for improving the quality of life of patients with age-related macular degeneration. This article reviews the literature and presents current data on RPET, identifies risk factors and mechanisms of its development, provides classification, and describes modern options for its diagnosis and treatment.

Antiangiogenic therapy for types I and II macular neovascularization in age-related macular degeneration

To conduct a retrospective analysis of the use of anti-VEGF therapy in AMD patients with types I and II of MNV. The study enrolled 89 AMD patients (89 eyes) with active MNV who have been under observation for 3 years. In the course of treatment all patients underwent standard ophthalmological examination that included visometry, biomicroscopy and ophthalmoscopy with mydriasis, as well as optical coherence tomography. Anti-VEGF therapy was found to stabilize best corrected visual acuity (BCVA) in both types of MNV (I and II). Comparison of the intraretinal and subretinal fluids (IRF and SRF) revealed that initially neuroepithelium detachment is more frequent (approximately in 90% of eyes) than IRF (30-40%). Antiangiogenic therapy is associated with better resorption of SRF, by the third year of the follow-up the neuroepithelium detachment is visualized in 60% of patients, while IRF remains and is observed in 40% of cases. Antiangiogenic therapy has shown good functional and morphological effectiveness in both first and second types of MNV.

Commentary: Acute central serous chorioretinopathy - Treat early, observe longer.

The understanding of central serous chorioretinopathy (CSCR) in terms of its pathophysiology and treatment has been evolving slowly over the past few decades. Due to its self-limiting course with good visual prognosis, historically the clinical observation for 3 months before any intervention, especially for the first episode, has been the gold standard of care.[1] But the patients suffer from blurred vision and metamorphopsia till the resolution of fluid, which is mostly till the third month from the onset. With the recent changes in the workplace demands for the younger population who are prone to this disease, the suboptimal visual acuity during the observation phase of treatment is a hindrance to their professional performance. Chronic CSCR reduces the quality of life significantly for the patients.[2] The need for an early intervention aiming for rapid resolution of the fluid is now warranted, and hence many approaches are being evaluated. In the current issue of the Indian Journal of Ophthalmology, an article evaluated the use of subthreshold green laser for treating CSCR and analyzed the improvement using multiple parameters including multifocal electroretinogram.[3] The prospective trial evaluated the use of subthreshold laser (STL) in acute CSCR, which was previously limited to treating chronic or recurrent episodes. It employed both objective and subjective parameters for analysis. STL aims to target the retinal pigment epithelium (RPE) while preserving the photoreceptors that are lost in the focal continuous-wave laser treatment. The proposed mechanism of STL is the absorption of radiation by melanin that induces heat shock proteins, which may, in turn, restore the RPE function.[4] This approach also supplements the pathophysiological hypothesis of hyperpermeable pachychoroid vessels that increase hydrostatic pressure leading to focal RPE detachments. The subsequent increase in hydrostatic pressure overwhelms the RPE leading to subretinal fluid (SRF) accumulation.[5] Improvement in RPE function may increase its pumping action leading to the resolution of SRF. The STL, though, needs careful titration as there is no visible endpoint that has been known to lead to undertreatment. Also, accidental delivery of threshold dose is known to occur. This makes the STL a controversial option to be utilized in CSCR with the foveal and juxtafoveal leaks. Off-label use of photodynamic therapy (PDT) for treating CSCR by initiating free radical-induced vascular remodeling reducing the vascular permeability is a preferred option to treat foveal leaks at many centers.[6] The first use of PDT was reported by Yannuzzi et al.[7] in chronic CSCR, since then it has been reported to also provide a faster SRF resolution with better recovery of retinal sensitivity in acute CSCR. Half-dose PDT has been shown to increase the likelihood of SRF resolution and improved visual outcome in a placebo-controlled prospective trial in cases of acute CSCR and has been proven to be as effective or superior to full-dose, half-fluence, or half-time PDT in both acute and chronic CSCR.[6] Half-dose PDT reduces the chances of systemic side effects of verteporfin, as well as angiogenic occlusion, reported rarely with full-dose PDT. Future trials thus should be undertaken to compare the effectiveness of STL with half-dose PDT rather than placebo as the aim of treatment with STL aligns more with PDT rather than observation. Recent landmark studies by Matsumoto et al.[8] and Spaide[9] have proposed vortex vein ampulla as the prime resistor of choroidal flow. These observations suggest that CSCR occurs secondary to congestion of vortex vessels, which in turn leads to a thick choroid. Subsequently, venovenous anastomoses formed among different vortex veins act as a decongestive mechanism. Chronic congestion and formation of pachyvessels cause compression of choriocapillaris and ischemia triggering pachychoroid neovasculopathy. Maturation of these vessels leads to polypoidal choroidal vasculopathy. While we aim to treat the patients of acute CSCR for resorption of SRF, the patients should be followed up for a lifetime with enhanced depth imaging with spectral-domain optical coherence tomography (OCT) or swept-source OCT to measure the choroidal thickness. The evolving professional demands for good visual acuity will soon be changing the treatment algorithm of CSCR. We congratulate the authors to complete and publish the study providing an objective parameter for the follow-up. Future comparative trials to evaluate various imaging or diagnostic markers and different treatment options will help the fraternity formulate new guidelines for the treatment.

Efficacy of Intravitreal Bevacizumab in Chronic Central Serous Chorioretinopathy in Terms of Mean Reduction of Central Macular Thickness in Pakistani Patients

Background: Central serous chorioretinopathy (CSCR) is an idiopathic condition described by serous neurosensory retinal detachment at the posterior pole, usually associated with serous retinal pigment epithelial detachment (PED). CSCR patients as a rule have good visual prognosis. In most of the patients, CSCR is self-limiting and patients regain the last visual acuity. However, some patients may have visual disability due to permanent RPE and photoreceptor damage. Objective: The objective of the study is to determine the effect of intravitreal Bevacizumab in cases of chronic central serous chorioretinopathy in terms of mean change in central macular thickness. Study Design: Interventional experimental study. Settings: The study was conducted in Department of Ophthalmology, Allied Hospital, Faisalabad Pakistan. Duration: 2 years from January 2017 to December 2018. Methodology: An aggregate of 95 cases were recruited for the study. Study included both male and female patients with diagnosis of chronic CSCR (at least 6month duration). Best corrected visual acuity, Intra Ocular Pressure on Goldman applanation Tonometer and Optical coherence tomography on Optovue were recorded of both eye of all patients. Before starting the treatment, informed consent was signed by every patient and they were called on the day of injection. Intravitreal off label Bevacizumab (1.25/0.05ml) was given through pars plana in operation theater under aseptic conditions. After injection topical antibiotic drops were given to patients for one week and patients called for follow up after one week, one month, 2 month and 3 months. Same parameters BCVA, IOP, Dilated fundus examine and OCT was recorded on every visit. The final outcome i.e., change in central macular thickness was recorded. Results: In this study, out of 95 cases, 53.68%(n=51) were between 30-45 years of age while 46.32%(n=44) were between 46-60 years of age, mean ± SD was calculated as 46.83+7.82 years, 74.74%(n=71) were male and 25.26%(n=24) were females. Pre-treatment mean central macular thickness was recorded as 344.77+14.61µ which reduced to 154.57+16.57 µ, mean difference was recorded as 190.2+21.46 µ, p value was 0.0001 showing a significant difference. Conclusion: We concluded that intravitreal Bevacizumab significantly reduced central macular thickness in cases of chronic central serous chorioretinopathy.