Outcomes of Retinal Pigment Epithelial Detachment in Vogt-Koyanagi-Harada Disease

IntroductionThe aim of this study was to report the clinical profile and outcomes of retinal pigment epithelial detachment (PED) in Vogt-Koyanagi-Harada (VKH) disease, and to evaluate the correlation between PED and the subsequent development of central serous chorioretinopathy (CSC) throughout the whole corticosteroid treatment course.materials and methodsA total of 470 eyes with VKH were reviewed, and 12 eyes with VKH and PED were recruited. Patients were divided into two groups according to the CSC onset or not throughout the whole course (CSC group and non-CSC group). Best-corrected visual acuity (BCVA) improvement, and PED angle (PEDA, the angle between the two lines of the vertex of the lifted retinal pigment epithelium to the two edge points of the Bruch membrane) were compared between the two groups.ResultsThe prevalence of PED and CSC in VKH was 2.55% (12/470) and 1.06% (5/470), respectively. BCVA improvement in the non-CSC group was greater than that in the CSC group, but without a statistical difference (P=0.25). PEDA was significantly smaller in the CSC group than in the non-CSC group (P=0.03).DiscussionPEDA is an ideal parameter to reflect hydrostatic pressure and stretches for RPE. As PED predisposes to the development of CSC in selected VKH eyes, PEDA may be a valuable predictive factor for the development of CSC in VKH patients.

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.

Bevacizumab simultaneous combined with dexamethasone implant for treatment of neovascular serous retinal pigment epithelial detachment secondary to neovascular age-related macular degeneration

Purpose: To evaluate the add-on effect of simultaneous intravitreal dexamethasone implant to bevacizumab for treatment of neovascular serous retinal pigment epithelial detachment (PED) secondary to neovascular age-related macular degeneration (nAMD). Methods: A 72-year-old male patient was previously treated with intravitreal bevacizumab and aflibercept for neovascular serous PED secondary to nAMD. Because of the recurrences in neovascular PED patient was treated with simultaneous intravitreal injection of bevacizumab and dexamethasone implant. Results: At the initial visit, the patient’s the best corrected visual acuity (BCVA) in the left eye was 20/800. His left eye had neovascular serous PED with a height of 1100 µm and a largest linear diameter of 3953 µm accompanied by subretinal fluid. He received four intravitreal bevacizumab and five intravitreal aflibercept injections. Although there was a decrease in PED sizes from time to time during the 16-month treatment period, PED height was 926 µm and PED greatest linear diameter was 5820 µm at the end of 16th month. Later, the patient could not have an injection for 3 months (he could not come to his controls during the pandemic period), and when he arrived 3 months later, the PED height was 910 µm and the greatest linear diameter was 5830 µm. With a single simultaneous intravitreal injection of bevacizumab and dexamethasone implant, the PED regressed to 168 µm in height after 3 months. The BCVA increased to 20/200. Any clinical toxic effects did not occur and intraocular pressure did not rise for 3 months after injection. Conclusion: Simultaneous intravitreal bevacizumab and dexamethasone implant injection effectively and safely treated treatment-resistant neovascular serous PED. This therapy may be a novel alternative therapy for treatment resistant neovascular serous PED secondary to nAMD. However, further studies are required to understand its effectiveness and safety.

Central Serous Chorioretinopathy: Multimodal Imaging and Management Options

Central serous chorioretinopathy (CSCR) is an idiopathic maculopathy characterized by thickened choroid, retinal pigment epithelial detachment, and variable subretinal fluid. CSCR predominantly affects young men, with risk factors including corticosteroid use, the type A behavior pattern, and psychological stress. While usually self-limited with a good visual prognosis, recurrent and persistent CSCR can lead to outer retinal and/or retinal pigment epithelial atrophy, choroidal neovascularization, and visual loss. This article reviews current multimodal imaging and treatment options, which include observation, mineralocorticoid receptor antagonists, thermal laser photocoagulation, and off-label photodynamic therapy with verteporfin.

A phase I, open-label, dose-escalation trial of BI 1701963 as monotherapy and in combination with trametinib in patients with KRAS mutated advanced or metastatic solid tumors.

TPS3651 Background: Activating mutations of KRAS drive many types of cancer. Activation of KRAS relies on guanine nucleotide exchange factors, such as SOS1, to mediate exchange of GDP for GTP. BI 1701963 is a small-molecule protein–protein interaction inhibitor that prevents the interaction between KRAS and SOS. Binding of BI 1701963 to the catalytic site of SOS1 inhibits binding of SOS1 to RAS–GDP, thereby hindering the exchange from RAS–GDP (inactive form) to RAS–GTP (active form). In preclinical studies this has been shown to lead to cytostasis in cancer cells addicted to KRAS signaling. Methods: NCT04111458 is a first-in-human trial of BI 1701963 in patients aged ≥18 years with tumors harboring KRAS mutations. Primary objectives are to determine the maximum tolerated dose (MTD) and recommended Phase II dose of BI 1701963 as monotherapy and in combination with trametinib, based on dose-limiting toxicities (DLTs). Secondary objectives are to evaluate safety, tolerability, pharmacokinetics/-dynamics and preliminary efficacy. The study will have two arms (mono- and combination therapy), and be divided into dose escalation (Part A), confirmation (Part B) and expansion (Part C, combination only) phases. Inclusion criteria include activating KRAS mutation, ≥1 evaluable lesion (RECIST 1.1), ECOG PS ≤1 and adequate organ function. Exclusion criteria include history of: RAS, MAPK or SOS1 targeting therapies; retinal vein occlusion; retinal pigment epithelial detachment; and decreased cardiac function. Parts B and C will be conducted in patients with advanced NSCLC. Treatment will continue until confirmed clinical benefit, defined toxicities, or withdrawal of consent. The primary endpoints are: Part A, the MTD, and the number of patients with DLTs during Cycle 1; Part B (monotherapy), the number of patients with DLTs; Part C, objective response (OR, RECIST 1.1). Starting doses of BI 1701963 in Part A will be 50 mg once daily (QD) orally (monotherapy) and 100 mg QD (combination, once proved safe as monotherapy) and will be escalated until the MTD is reached. The starting dose of trametinib will be 1 mg QD, escalated to the MTD or a max. of 2 mg QD. Dose cohorts will include ≥3 patients, with two therapeutic relevant doses (TRDs) established in each arm. In Part B, patients will be randomized to groups receiving one of the TRDs. If an OR is observed at a TRD in the combination arm, additional patients will be recruited into expansion cohorts receiving the relevant dose. As of Feb 11, 2020 three patients have been treated. Clinical trial information: NCT04111458 .

A Case of Pneumatic Displacement with Gas Tamponade Performed for Macular Subretinal Hemorrhage Complicating Vogt-Koyanagi-Harada Disease

We experienced a case of subretinal hemorrhage (SRH) from choroidal neovascularization (CNV) complicating Vogt-Koyanagi-Harada disease (VKH) that underwent pneumatic displacement of hematoma by intravitreal gas injection. A 76-year-old male revealed VKH relapses and optical coherence tomography showed irregular retinal pigment epithelium in his right eye and serous retinal detachment and retinal pigment epithelial detachment in his left eye. Fluorescein angiography of the left eye showed hyperfluorescence possibly attributable to CNV. One month later, SRH occurred in the left eye, yet it was spontaneously absorbed. However, approximately 1 year later, the SRH recurred in the left eye affecting a wide area, including the macular region, and his visual acuity (VA) decreased to 0.06. When pneumatic displacement of the hematoma by intravitreal gas injection was performed, the SRH was inferiorly displaced, and his VA improved to 0.4. Pneumatic displacement with gas tamponade was effective for treating a case of SRH caused by persistent CNV complicating VKH.

Avascular Retinal Pigment Epithelial Detachment Treated With Intravitreal Ranibizumab: Three Year Follow Up

Retinal pigment epithelial detachment (PED) is a common manifestation in several retinal conditions including age-related macular degeneration1. Based on retinal imaging as well as clinical examination, PEDs can be classified as drusenoid, serous or vascular2,3,4. Vascularised PEDs, as the name suggests, are associated with choroidal neovascularization (CNV). Drusenoid and serous PEDs may or may not have an associated CNV. Anti-VEGF therapy has a well proven role in the treatment of vascularized PED5,6. Less well established is the beneficial effect of anti-VEGF therapy in those PEDs where a CNV is not clearly present. Large serous PEDs were excluded from phase 3 clinical trials such as TAP, ANCHOR and MARINA7,8,9 trials . As such these trials cannot be relied upon to provide management strategies for these lesions. Development of a rip in a PED can result in permanent damage to central vision10,11.Such a rip is often spontaneous although intravitreal therapy can also precipitate an RPE rip12,13. It is therefore desirable to reduce the height of a PED in order to minimize the risk of a rip. Furthermore a longstanding PED presumably interferes with the nutrition to the RPE and photoreceptors and thus early flattening of the PED or reducing its height was an important treatment rationale in this study. No universally agreed guidelines exist on the treatment of PEDs not associated with a CNV. One study14 looked specifically at the role of the anti-VEGF agent Ranibizumab (Lucentis) in non-vascularised PEDs but the follow-up period in that study was 12 months. The purpose of this study is to look at the long term effects of 3 Ranibizumab injections given in eyes with non-vascularised PEDs . The effects were monitored for up to 36 months and to date this is the longest follow-up published for this sub-set of treated patients.

A Case of Giant Macular Hole Progression after Rupture of a Giant Retinal Pigment Epithelial Detachment

We report a case of giant macular hole progression after rupture of giant retinal pigment epithelial detachment (PED). The patient was a 91-year-old man who had a giant PED in the left eye. He had bilateral hypermetropia (+2.00 dpt), and he had developed posterior vitreous detachment. The PED was 5,800 μm in diameter and 800 μm in height and ruptured during follow-up. A macular hole was formed, with a diameter of 400 μm, and the height of the PED had reduced to 360 μm. After 5 months, the macular hole expanded up to a diameter of 600 μm. Therefore, some cases of giant PED may lead to macular hole.