Evolution of Polypoidal Lesions after Treatment of Polypoidal Choroidal Vasculopathy.

Purpose: To evaluate the status and evolution of polypoidal lesions during the course of treatment of patients with symptomatic macular polypoidal choroidal vasculopathy (PCV). Design: Comparative cohort study of randomly selected patients from a multicenter, randomized controlled clinical trial. Participants: Thirty randomly selected patients from the EVEREST II study who were treated with combination ranibizumab and verteporfin photodynamic therapy (n = 15) or ranibizumab monotherapy (n = 15). Methods: All patients were randomized at baseline and treated with a standardized treatment protocol. Indocyanine green angiography (ICGA) images were graded at the central reading center at baseline and months 3, 6, 12, and 24. Polypoidal lesions present at baseline were overlaid on ICGA images at subsequent visits to determine if these remained perfused or had regressed completely. New polypoidal lesions occurring at subsequent visits were similarly tracked to detail the evolution of each polypoidal lesion. Main Outcome Measures: Complete polypoidal lesion regression over time. Results: Complete polypoidal lesion regression was higher in the combination therapy group compared with the monotherapy group at all visits (month 12, 12 of 15 patients [80%] vs. 5 of 14 patients [35.7%]; P = 0.016). Persistence of baseline polypoidal lesions was lower in the combination therapy group: 1 of 15 patients (6.7%) versus 7 of 14 patients (50%) in the monotherapy group at month 12. Recurrences of polypoidal lesions that had regressed completely at an earlier time point were uncommon: 0% in the combination therapy group and 1 patient each at months 6 and 12 in the monotherapy group. Fewer new polypoidal lesions (arising after the baseline visit) were found in the combination therapy group at all visits (combination therapy: 2 of 15 [13.3%] vs. monotherapy: 4 of 14 eyes [28.6%] at month 12). Total polypoidal lesion area was significantly smaller in the combination therapy group compared with the monotherapy group throughout the study (0.013 mm2 vs. 0.110 mm2; P < 0.01 at month 12). Conclusions: Combination therapy was associated with higher rates of complete polypoidal lesion regression and fewer persistent polypoidal lesions compared with monotherapy. Closed polypoidal lesions rarely reopened, regardless of the treatment.

Comparison of Polypoidal Choroidal Vasculopathy Lesion Sizes Measured on Multicolor Imaging and Indocyanine Green Angiography.

Purpose: To evaluate the areas of lesion components of polypoidal choroidal vasculopathy (PCV) measured using multicolor imaging compared to indocyanine green angiography (ICGA). Methods: In a prospective study of 50 consecutive treatment-naïve PCV patients, multicolor imaging and ICGA were performed. The images were independently graded by reading center-certified retinal specialists to confirm the diagnosis of PCV and identify lesion components. The areas of the respective lesion components were compared. Results: The mean age of the participants was 67.8 years. PCV was diagnosed in 96% of eyes using multicolor imaging. The mean numbers of polypoidal lesions identified using ICGA and multicolor were 4.0 and 2.1, respectively (P < 0.001), with mean total polypoidal lesion areas of 0.32 mm2 versus 0.30 mm2 (P = 0.727). The area of the branching vascular network (BVN) on ICGA was 7.8 mm2 compared to 5.7 mm2 on multicolor imaging (P = 0.289). Patients with four or more polypoidal lesions on ICGA had larger differences in total lesion area between ICGA and multicolor imaging (4.07 vs. -0.70 mm2, p = 0.039). Those with total lesion area ≥ 2.0 mm2 on ICGA had larger differences in mean polypoidal lesion number compared to those with smaller areas (2.2 vs. 0.5; P = 0.026). Conclusions: Multicolor imaging is a useful, noninvasive adjunct for detecting PCV lesion components, revealing lesion areas similar to but generally smaller than those seen on ICGA. This is important to consider when making treatment decisions with different imaging modalities. Translational Relevance: New features seen on multicolor imaging can aid in the diagnosis and treatment of PCV.

Acute Onset of Bilateral Follicular Conjunctivitis in two Patients with Confirmed SARS-CoV-2 Infections.

PURPOSE: To report bilateral follicular conjunctivitis in two confirmed Coronavirus (COVID-19) patients with the presence of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) in conjunctival swab specimens. PARTICIPANTS AND METHODS: Two unrelated patients with confirmed SARS-CoV-2 infection and bilateral acute conjunctivitis were examined. Conjunctival swabs were assessed for the presence of SARS-CoV-2 by quantitative real-time polymerase chain reaction (RT-PCR) and viral culture. RESULTS: Both patients developed eye redness 3 days after the onset of COVID-19 symptoms. Slit lamp examination showed bilateral acute follicular conjunctivitis, which was resolved within 6 days. RT-PCR demonstrated the presence of viral RNA in conjunctival specimens from both eyes, which was unrelated to viral RNA from throat swabs. CONCLUSION: SARS-CoV-2 may cause ocular manifestations such as viral conjunctivitis. Conjunctival sampling may be useful for infected patients with conjunctivitis and fever. Precautionary measures are recommended when examining infected patients throughout the clinical course of the infection.

Predictors of persistent disease activity following anti-VEGF loading dose for nAMD patients in Singapore: the DIALS study.

BACKGROUND: To determine the frequency of persistent disease activity following 3 loading doses of anti- vascular endothelial growth factor (VEGF) agents, and the anatomic and demographic predictors of early persistent disease activity among patients with neovascular age-related macular degeneration (nAMD). METHODS: In a retrospective real-world cohort study, 281 consecutive patients with nAMD were reviewed at baseline and after 3 anti-VEGF injections for pre-defined indicators of disease activity. Optical coherence tomography (OCT) features such as subretinal fluid, intraretinal cysts and intraretinal fluid were assessed by reading-center certified graders. Multiple logistic regression was performed on demographic and anatomic factors. RESULTS: At month 3, 66.1% of patients had persistent disease activity. The best-corrected visual acuity (BCVA) improvement was 0.16 LogMAR for those with no disease activity compared to 0 for patients with persistent activity (p < 0.001). The significant risk factors for persistent activity at 3 months were male gender (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.32-0.93, p = 0.025), intraretinal cysts at baseline (OR 2.95, 95% CI 1.67-5.20, p < 0.001) and subretinal fluid at baseline (OR 3.17, 95% CI 1.62-6.18, p = 0.002). At 3 months, 58% of patients had features of activity on OCT. Patients with intraretinal cysts and intraretinal fluid at baseline had worse BCVA at month 3 compared to patients without these OCT features (0.69 vs. 0.43, p < 0.001, and 0.62 vs. 0.43, p < 0.001, respectively). CONCLUSIONS: In a real-world study, 66.1% of nAMD patients have persistent disease activity after the initial loading dose, with poorer BCVA compared to those without. Baseline OCT features (intraretinal cysts and subretinal fluid) are useful predictors of persistent disease activity at month 3.

Sustainable practice of ophthalmology during COVID-19: challenges and solutions.

PURPOSE: The Coronavirus (COVID-19) outbreak is rapidly emerging as a global health threat. With no proven vaccination or treatment, infection control measures are paramount. In this article, we aim to describe the impact of COVID-19 on our practice and share our strategies and guidelines to maintain a sustainable ophthalmology practice. METHODS: Tan Tock Seng Hospital (TTSH) Eye Centre is the only ophthalmology department supporting the National Centre for Infectious Diseases (NCID), which is the national screening center and the main center for management of COVID-19 patients in Singapore. Our guidelines during this outbreak are discussed. RESULTS: Challenges in different care settings in our ophthalmology practice have been identified and analyzed with practical solutions and guidelines implemented in anticipation of these challenges. First, to minimize cross-infection of COVID-19, stringent infection control measures were set up. These include personal protective equipment (PPE) for healthcare workers and routine cleaning of "high-touch" surfaces. Second, for outpatient care, a stringent dual screening and triaging process were carried out to identify high-risk patients, with proper isolation for such patients. Administrative measures to lower patient attendance and reschedule appointments were carried out. Third, inpatient and outpatient care were separated to minimize interactions. Last but not least, logistics and manpower plans were drawn up in anticipation of resource demands and measures to improve the mental well-being of staff were implemented. CONCLUSION: We hope our measures during this COVID-19 pandemic can help ophthalmologists globally and serve to guide and maintain safe access in ophthalmology clinics when faced with similar disease outbreaks.

Multicolor Fundus Imaging of Polypoidal Choroidal Vasculopathy.

PURPOSE: Polypoidal choroidal vasculopathy (PCV) is a variant of neovascular age-related macular degeneration with distinct phenotypes, treatment, and visual prognosis. Multicolor imaging is a novel noninvasive imaging method that enables visualization of structures located at different layers of the retina and may be useful in detecting features of diseases. The features of PCV seen on multicolor imaging have not been studied. We aimed to describe the features of PCV detected using multicolor imaging and to compare these with standard color fundus photography (CFP). DESIGN: Hospital-based, cross-sectional study. PARTICIPANTS: Fifty consecutive treatment-naive patients diagnosed with PCV seen in a tertiary referral center. METHODS: Multimodal imaging was performed using standardized protocols, and included CFP, multicolor imaging, fluorescein angiography, and indocyanine green angiography (ICGA). The CFP and ICGA images were independently graded by reading center-certified retinal specialists to confirm the diagnosis of PCV and identify lesion components. The features of the lesion components seen on multicolor images were compared with those detected using CFP and ICGA. MAIN OUTCOME MEASURES: Frequency and features of lesions associated with PCV, specifically, polyps, branching vascular network (BVN), pigment epithelial detachments (PEDs), hemorrhages, and drusen. RESULTS: The mean age of the 50 participants was 67.9 years, and 60% were male. Polyps were most clearly seen on the infrared reflectance image and detected in 49 of 50 eyes (98%), appearing as dark gray oval lesions with distinct margins. On the multicolor composite images, polyps appeared as dark green oval lesions. The BVN appeared as mottled gray regions on infrared reflectance imaging and were seen less frequently compared with polyps (30/50 eyes, 60%). The margins of the BVN were less distinct compared with polyps. Other clinical features detected using multicolor imaging included PEDs (26%), subretinal hemorrhages (40%), and drusen (66%). CONCLUSIONS: Multicolor imaging is able to detect polypoidal lesions in most patients with PCV. The appearance of PCV lesions on multicolor imaging differs from standard CFP, although the location and shape of lesions correlate well with features seen on CFP and ICGA. Multicolor imaging is a useful, noninvasive adjunct to detect features suggestive of PCV, which may prompt definitive investigations such as ICGA.

EVEREST study report 4: Fluorescein angiography features predictive of polypoidal choroidal vasculopathy.

IMPORTANCE: It is important to identify features of polypoidal choroidal vasculopathy (PCV) that differentiate it from typical neovascular age-related macular degeneration (nAMD) on various imaging modalities, including fluorescein angiography (FA). BACKGROUND: PCV was thought to be indistinguishable from nAMD using FA alone. In real-world practice, indocyanine-green angiography may often be unavailable or contraindicated. DESIGN: Analysis of FA images from a prospective, multicentre study. PARTICIPANTS: Study images of both PCV and nAMD patients from the EVEREST study. METHODS: FA features at baseline were independently graded by masked graders (fellowship-trained ophthalmologists) using standardized diagnostic algorithms. MAIN OUTCOME MEASURES: Predictive indicators (sensitivity, specificity, positive and negative predictive values) for PCV. RESULTS: Of the 95 patients screened, 61 had PCV. Of the 34 screening failures, 15 were diagnosed as nAMD. Hyperfluorescent nodules on FA were observed in 80% of patients with PCV vs 20% with nAMD (P < 0.001). Blocked fluorescence on FA, which corresponded to the presence of subretinal haemorrhage, occurred more frequently among patients with PCV vs nAMD (61.7% vs 13.3%, P = 0.001). Similarly, the leakage characteristic of occult choroidal neovascularization occurred more frequently among patients with PCV vs nAMD (95.0% vs 73.3%, P = 0.026). The positive predictive value for PCV was 94.1% for hyperfluorescent nodules, 94.9% for blocked fluorescence, 83.8% for occult choroidal neovascularization and 82.0% for pigment epithelial detachment. CONCLUSIONS AND RELEVANCE: This study demonstrated that certain FA features can be predictive of PCV and may be considered as an indication for retina specialists to perform indocyanine green angiography as confirmatory test.

Multicolour imaging for the detection of polypoidal choroidal vasculopathy and age-related macular degeneration.

IMPORTANCE: Multicolour is a new imaging technology and its sensitivity for detecting polypoidal choroidal vasculopathy (PCV) and age-related macular degeneration (AMD) has not been well described. BACKGROUND: To evaluate the accuracy of multicolour imaging compared to colour fundus photography (CFP) in differentiating AMD and PCV from normal eyes, and in detecting PCV. DESIGN: Prospective cohort study at a tertiary referral centre. PARTICIPANTS: Fifty consecutive patients with PCV or AMD. METHODS: Standardized multimodal imaging, including CFP, multicolour imaging, and fluorescein and indocyanine green angiography, were graded by a Central Reading Center using standardized grading protocols. MAIN OUTCOMES AND MEASURES: Sensitivity, specificity, positive and negative predictive values (PPV and NPV). RESULTS: Of 100 eyes, 44 had PCV, 33 had AMD, and 23 were normal. Multicolour imaging had higher specificity (73.9% vs 52.2%) and NPV (94% vs 85.7%) compared to CFP for detecting all types of AMD. For the detection of PCV, multicolour had higher sensitivity (86.4% vs 59.1%) and NPV (89.3% vs 74.3%). Polypoidal lesions were detected in 39 of 44 eyes (88.6%) using multicolour imaging, while the branching vascular network (BVN) was detected in 16 of 44 eyes (36.4%). Using BVN as a parameter, infrared imaging specificity and PPV for detecting PCV were 96.6% and 88.9%, respectively. CONCLUSIONS AND RELEVANCE: Multicolour imaging is superior to standard CFP in differentiating AMD and PCV from normal eyes, and in detecting features of PCV. Specific features seen on multicolour imaging can alert ophthalmologists to the likely presence of these diseases so that additional definitive investigations can be performed.

EVEREST Report 5: Clinical Outcomes and Treatment Response of Polypoidal Choroidal Vasculopathy Subtypes in a Multicenter, Randomized Controlled Trial.

Purpose: The purpose of this study was to describe the characteristics of polypoidal choroidal vasculopathy (PCV) subtypes among patients from a multicenter randomized controlled trial and to determine the impact of PCV subtypes on clinical outcomes. Methods: This was a prospective cohort study of 61 patients with macular PCV from the EVEREST study. Indocyanine green (ICGA) and fluorescein angiography (FA) obtained using standardized imaging protocols were graded to classify PCV into three subtypes. Type A PCV had polyps with interconnecting channels, type B had polyps with branching vascular networks, but no significant leakage on FA, and type C had polyps with branching vascular networks and leakage on FA. The best-corrected visual acuity (BCVA) and proportion of patients with BCVA ≥ 20/40 were compared among the three PCV subtypes. Results: Of the 61 patients, 54 were gradable for PCV subtype. Among these, 8 had type A PCV (14.8%), 27 had type B (50%), and 19 had type C (35.2%). At baseline, BCVA was 67.1 letters for type A, 58.7 for type B, and 43.5 for type C (P < 0.001). At 6 months, BCVA was highest among patients with type A compared with types B and C (80.1 letters versus 67.2 versus 50.4, respectively; P < 0.001). Type A PCV gained 13 letters compared with 8.5 (type B) and 6.9 (type C). BCVA ≥ 20/40 was highest for type A compared with types B and C (100% vs. 51.9% vs. 10.5%; P < 0.001). On performing ANCOVA, PCV subtype and baseline BCVA significantly affected final BCVA. Conclusions: The visual outcome following treatment varies with PCV subtype classification. The distinction in clinical outcomes between the PCV subtypes is observed in the initial months following the start of treatment.