Anti-Vascular Endothelial Growth Factor for the Management of Peripapillary Choroidal Neovascular Membrane: A Systematic Review

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Methods Medline, Embase and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched between January 2000 and December 2024 for relevant articles that used anti-VEGF therapy to treat pCNVM of any origin. This review followed PRISMA guidelines and was prospectively registered (PROSPERO registration number CRD42024551949). Results Ten studies reporting on 269 eyes were included. Eight studies used a pro re nata (PRN) strategy, 1 study used a loading phase followed by an as-needed phase and 1 study used a fixed schedule strategy. There was a mean of 7 injections required. Eight studies reported improvements in best corrected visual acuity (BCVA) at final follow-up following treatment. The mean logarithm of the minimum angle of resolution (logMAR) change was 0.092, or approximately one line Snellen improvement. Two studies reported on macular thickness, and one reported on choroidal thickness after treatment, all of which noted decreased thickness at final follow-up. No significant complications were reported. Conclusions For patients with pCNVM of various etiologies, anti-VEGF injections using any treatment strategy, including conservative management with a PRN approach, seems to be a safe and effective therapy associated with improved visual acuity. Figures Figure 1 Introduction Peripapillary choroidal neovascular membrane (pCNVM) is an uncommon subtype of choroidal neovascularization, representing approximately 10% of all cases.( 1 ) pCNVM are seen in a variety of underlying diagnoses: degenerative conditions (AMD, angioid streaks, and pathological myopia); inflammatory pathologies (chronic uveitis, including Vogt–Koyanagi–Harada syndrome (VKH), ocular tuberculosis, and toxoplasmosis); optic nerve disorders (papilledema, tilted optic disc syndrome, optic nerve drusen); neoplastic disorders (choroidal naevi, osteoma); vascular disorders (polypoidal choroidal vasculopathy).( 2 , 3 ) For between 17 and 39% of cases, however, the exact cause of pCNVM remains unidentified, leading to the classification of these cases as idiopathic.( 4 – 6 ) Compared to other locations of CNVM, pCNVM is more likely to be idiopathic.( 6 ) Furthermore, compared to neovascularization at other locations, the visual significance of pCNVM varies. As many as two-thirds of cases of pCNVM remain asymptomatic, with the membrane restricted to the extrafoveal location.( 7 , 8 ) Patients may, however, present with significant visual disturbances due to the extension of the membrane to the fovea or due to the presence of subretinal fluid. (5) pCNVM may mimic disc edema, central serous chorioretinopathy, chronic inflammatory lesions, and optic disc neovascularization associated with ischemic or vascular diseases. Historically, the primary treatment options available for pCNVM have included surgery, laser photocoagulation, photodynamic therapy, and intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections.( 3 ) For choroidal neovascularization at any location, anti-VEGF therapy is the most commonly used therapeutic modality.( 7 ) Compared to macular CNVM, functional visual changes experienced by patients with pCNVM may vary and thus may warrant a different treatment approach.( 9 ) The guidance on pCNVM specifically is limited compared to that for choroidal neovascularization in other locations. The purpose of this systematic review is to outline ( 1 ) the visual and anatomical outcomes associated with the use of various anti-VEGF drugs for treatment of pCNVM and ( 2 ) the possible treatment regimens used, providing a comprehensive understanding of the effectiveness of each. Methods An electronic search strategy was developed in consultation with an experienced medical information specialist (Supplemental Material 1). We used this strategy to search Ovid MEDLINE, Ovid EMBASE, and CINAHL databases from their January 2000 to December 2024. The study protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO 2024, registration number, CRD42024551949). All results were exported to Covidence (Veritas Health Innovation, Melbourne, Australia), where duplicates were removed. For primary study selection, titles and abstracts from the initial search were screened by two independent reviewers (AH and AS) using established eligibility criteria. For secondary study selection, the full texts of selected studies were assessed by two independent reviewers (AH and AS) against the eligibility criteria. An explanation was provided for the excluded full texts. Any disagreement between reviewers regarding the inclusion of a study was resolved through consensus. This review included any study that explored the clinical outcomes of patients with pCNVM after intravitreal anti-VEGF injections. Experimental and observational studies were included. Studies had to contain original data, and reviews and editorials were excluded. Patients receiving combined therapy of anti-VEGF injection in conjunction with other therapies such as photodynamic laser, or laser photocoagulation were excluded. Case reports, conference abstracts and non-English studies were excluded. There were no restrictions for the year of publication. Data extraction was conducted using a tool that included key elements listed in Supplemental Material 2. Two independent reviewers (AH and AS) extracted data from studies and discrepancies were resolved through consensus. Descriptive statistics were used to summarize findings. The risk of bias (RoB) for case series was assessed using the Joanna Briggs Institute (JBI) critical appraisal tool for case series. The tool addresses the internal validity and risk of bias of case series designs, addressing confounding, selection, and information bias, in addition to the importance of clear reporting.( 10 ) The risk of bias (RoB) for cohort studies was assessed using the Newcastle Ottawa RoB assessment scale, which assesses studies in the domains of patient selection, comparability of the cohorts and outcome measures.( 11 ) The selection domain could receive a maximum of four stars, comparability could receive a maximum of two stars, and outcome could receive a maximum of three stars. Results PRISMA results The search yielded 274 results. Following deduplication, 193 studies underwent title/abstract screening of which 36 full texts were reviewed. Ultimately, 10 full texts were included in this study. The PRISMA flow diagram is shown in Fig. 1 . Demographics Two hundred and sixty-nine eyes of 256 patients were included in this review. The mean age of the included participants was 68 years and the cumulative percentage of female patients across the studies was 53% and the percentage male was 47%. The percentage female and the mean age for each study is reported in Table 1 . Study Designs, Locations, Time Periods and Risk of Bias Assessments The included studies took place between 2003 and 2023. Three of the studies were conducted in India and two studies were conducted in Israel. The remaining five studies were conducted in Spain, Germany, the United States, Lebanon, and Switzerland. Nine of the studies were case series and one study was a retrospective cohort study. The RoB assessments are shown in Supplemental Tables 2 and 3. Amongst the case series, there was an overall low risk of bias with the mean score being nine out of ten. The retrospective cohort study showed an intermediate risk of bias with a score of six out of nine, given the lack of a control group. Table 1 Baseline characteristics of included studies and patients Study Number of patients Number of eyes Percentage Female Mean Age Etiology Study Location D'souza 2018 (2) 8 8 63% 46 Inflammatory India Figueroa 2008( 9 ) 5 6 60% 71 AMD, angioid streaks, idiopathic Spain Hoeh 2009 10 4 4 25% 79 AMD, idiopathic Germany Lin 2019 5 27 33 45% 82 AMD USA Mansour 2008 11 8 8 62% 39 Inflammatory Lebanon Ozgonul 2019 12 6 6 20% 46 IIH Switzerland Rabina 2022 13 30 30 63% 84 AMD Israel Roy 2017 14 28 30 32% 37 Inflammatory India Singh 2020 15 74 77 57% 62 Idiopathic, AMD, inflammatory, angioid streaks, IIH, choroidal rupture, optic nerve head drusen India Stanescu 2023 16 66 67 58% 82 AMD Israel Etiology of pCNVM in Included Patients Across the studies, patients with various etiologies of pCNVM were included. Six studies examined a total of 163 eyes with age-related macular degeneration (AMD), while four studies included 56 eyes with pCNVM of inflammatory etiologies. Three studies included 29 eyes of patients with idiopathic pCNVM and two studies included 9 eyes of patients with angioid streaks. One study reported on 6 eyes with idiopathic intracranial hypertension (IIH), and another study documented one eye each with choroidal rupture and optic nerve head drusen. Anti-VEGF Drug and Treatment Strategy Used Two hundred and fifteen eyes received bevacizumab, 41 eyes received aflibercept and 22 eyes received ranibizumab. Note that some patients were started on one agent but switched to another. Eight studies used a pro re nata (PRN) strategy, one study used a 3-injection loading phase followed by a PRN phase( 12 ) and one study used a fixed schedule strategy.( 8 ) Number of Injections Administered and Follow-up Across Studies Across the studies, a mean of 7 injections were administered, but the mean number of injections in each study ranged from 2 to 14. In the studies using a PRN treatment strategy, there was a mean of 6 injections given to patients. For the study using the 3-injection loading phase followed by PRN therapy, there was a mean of 7 injections used. For the study using a fixed interval treatment strategy, there was a mean of 3 injections administered. The mean follow-up across studies was 34 months, with a range of 3 months to 44 months. Visual Acuity Changes Eight of the ten studies reported an improvement in patients’ visual acuity at final follow-up after treatment, with two studies reported worse visual acuities compared to baseline and final follow-up. Across all studies, the mean logMAR change in visual acuity following treatment was 0.092, or approximately one Snellen line of improvement. The change in visual acuity for each study is reported in Table 2 . Four of the studies showed a statistically significant improvement in vision after treatment, and one study showed a non-statistically significant improvement in vision. Three studies did not report on the statistical significance of the improved visual acuity. One study showed a statistically significant decrease in vision at final follow-up and one study reported a non-statistically significant decrease in vision. Among the patients treated with a PRN strategy, the change in visual acuity ranged from a decrease in vision by -0.19 (equivalent to a loss of approximately 2 Snellen lines) to a gain in vision by 0.31 (equivalent to an improvement of approximately 3 Snellen lines) on the logMAR scale. The mean change in visual acuity for those patients treated using a PRN strategy was an improvement of 0.08. In the study where patients were treated with a loading phase followed by a PRN phase( 12 ), there was a decrease in logMAR visual acuity by 0.1. In the study where patients were treated with a regular dose, in which all cases were due to AMD, there was an increase in visual acuity by 0.29. Choroidal and Macular Thickness Changes Two of the studies, D’Souza 2018 and Singh 2020, measured macular thickness.( 2 , 13 ) Both studies found a decrease in macular thickness, with a mean decrease in macular thickness of 138.9 µm. Singh 2020 reported that this was a statically significant decrease (p < 0.001), while D’Souza 2018 did not report p values. Singh 2020 measured choroidal thickness( 13 ) and found a non-statistically significant decrease in choroidal thickness after injection, with a mean decrease of 41 µm (p = 0.2). Recurrence Across the studies, 6 studies reported on the rate of recurrences. Among these studies, 2 studies reported that none of the patients had a recurrence within the study follow-up period (0% recurrence rate). The remaining four studies had a recurrence rate of between 13 and 85%. Across the studies reporting on recurrences, the mean recurrence rate was 54%. The etiologies of the cases that recurred were inflammatory (n = 6), AMD (n = 12) and angioid streaks (n = 1). Among the 4 studies reporting that patients had a recurrence, the mean recurrence occurred at 8 months following initial treatment. One study, however, reported that recurrence occurred as early as 3 months or as late as 74 months after initial injection. Only one study commented on visual acuity at recurrence, noting that there was a one line drop in visual acuity upon recurrence. Two studies reported on the mean number of injections required following recurrence, with one study reporting as many as 6 injections required and the other study reporting the need for only one injection after recurrence. Even after recurrence, however, patients generally had an improvement in final visual acuity after a follow up injection (Table 2 ). Complications Across the studies, there were no reports of adverse events associated with the use of anti-VEGF therapy for the treatment of pCNVM. Table 2 – Anti-VEGF drug, treatment strategy, number of doses and visual acuity changes of the included studies Study Drug Treatment strategy Mean Doses Mean Baseline BCVA Mean Final BCVA Mean Change in BCVA P values D'souza 2018( 2 ) Bevacizumab and Ranibizumab as needed 2.75 0.82 ± 0.96 0.51 ± 0.44 0.31 p < 0.0001 Figueroa 2008( 9 ) Bevacizumab as needed 4.2 0.375 ± 0.222 0.18 ± 0.15 0.195 Not reported Hoeh 2009( 14 ) Bevacizumab as needed 3.5 0.65 ± 0.53 0.5 ± 0.44 0.15 Not reported Lin 2019( 8 ) Bevacizumab and Aflibercept regular dose 3 0.51 ± 0.34 0.30 ± 0.28 0.21 p = 0.294 Mansour 2008( 15 ) Bevacizumab as needed 1.1 0.82 ± 0.36 0.47 ± 0.38 0.35 p = 0.01 Ozgonul 2019( 16 ) Bevacizumab, Ranibizumab and Aflibercept as needed 2 1.24 0.95 0.066 Not reported Rabina 2022( 12 ) Bevacizumab Loading phase followed by as-needed 7.2 0.46 ± 0.62 0.56 ± 0.78 -0.1 p = 0.28 Roy 2017( 17 ) Bevacizumab and Ranibizumab as needed 2.76 0.60 ± 0.49 0.40 ± 0.49 0.2 p = 0.083 Singh 2020( 13 ) Bevacizumab, Ranibizumab and Aflibercept as needed 4.9 0.55 ± 0.54 0.29 ± 0.39 0.26 p < 0.001 Stanescu 2023( 18 ) Bevacizumab as needed 14 0.53 ± 0.54 0.72 ± 0.59 -0.19 p < 0.01 Discussion This systematic review has demonstrated that intravitreal anti-VEGF injections are an effective treatment strategy for pCNVM, leading to improvements in visual acuity and macular thickness. Patients with various etiologies of pCNVM, including AMD, inflammatory conditions, idiopathic cases, and others, benefited from anti-VEGF therapy. Although the included studies varied in terms of the specific anti-VEGF agent used, treatment strategy, and follow-up duration, the overall outcomes suggest that anti-VEGF injections are a favorable treatment in the management of pCNVM. From a long-term visual acuity perspective, conservative treatment strategies, like a PRN approach, are successful in the management of this disease. Anti-VEGF therapy appears to be an effective therapy for the management of pCNVM of many etiologies and is the most commonly used treatment strategy, however, other therapeutic modalities exist. Surgery has historically been used, but the advent of less invasive treatments has significantly reduced its role in management.( 19 ) Photodynamic therapy, is another treatment that has been used for the treatment of CNVM, however it cannot be done over the nerve and may cause visual disturbances following treatment.( 20 , 21 ) Laser photocoagulation is another treatment option for the treatment of extrafoveal choroidal neovascularization and has shown long-term benefits in visual acuity, however, is not as commonly used as anti-VEGF therapy due to potential decreases in vision in the short term .( 22 ) The majority of the included studies reported an improvement in visual acuity following anti-VEGF therapy. There was mean improvement of one Snellen line across all studies was 0.092, indicating an overall modest visual gain. Additionally, studies measuring macular thickness found a statistically significant reduction, suggesting that anti-VEGF therapy not only improves visual function but also has a beneficial effect on the structural characteristics of the retina. Despite the variability in treatment strategies—including pro re nata (PRN), loading doses followed by PRN, and fixed schedules—most patients showed improved outcomes. The variability in treatment regimens reflects the lack of a standardized approach to managing pCNVM. While some studies used a PRN strategy, administering injections only when needed, others employed a fixed regimen, or a loading phase followed by PRN treatment. The mean number of injections varied, with a range from 2 to 14 across different studies, highlighting the need for a tailored approach based on individual patient responses and the etiology of pCNVM. Importantly, this review found that anti-VEGF therapy was generally safe, with no serious complications reported across the included studies. It is also interesting to note that conservative treatment strategies, such as a PRN approach, ultimately resulted in good final visual acuity despite possible short-term decreases in vision upon membrane recurrence between doses. This review included the treatment of many disease etiologies. Interestingly, approximately 40% of pCNVM cases are idiopathic.( 6 ) Only three of the ten studies included in this review addressed this important subgroup of patients.. Given the most common etiologies of pCNVM, it is important to rule out degenerative pathology, inflammatory causes, vascular causes, optic nerve disorders, and neoplastic disorders before concluding that a case of pCNVM is idiopathic. The limited evidence from the three studies including idiopathic cases (involving 29 eyes), showed that anti-VEGF injections were effective for the management of idiopathic pCNVM with improvements in visual acuity. Only one study reported on the structural changes in idiopathic patients noting no changes in the macular or choroidal thickness following anti-VEGF injections.( 13 ) A limitation of this review is the lack of experimental trials. Of the ten included studies, nine studies were case series. Although these case series were of high quality, none of the existing evidence compares treatments in a prospective and standardized manner through comparative studies. Furthermore, the variability in treatment strategies, follow-up durations, and patient populations across the studies introduces heterogeneity, complicating direct comparisons and the establishment of a standardized treatment protocol for pCNVM. Furthermore, an inherit limitation of the systematic review is the heterogeneity of studies, with studies originating from a diverse group of countries and settings. However, this heterogeneity can also enhance the generalizability of findings, as the consistent trend of treatment efficacy across varied populations suggests broader applicability. While a meta-analysis was not feasible due to the heterogeneity in study designs, populations, and outcomes, we employed a narrative synthesis to systematically compare and contrast key differences and similarities across studies, providing a comprehensive understanding of the evidence base. Another limitation of this review is the follow-up period of the included studies. The mean duration of follow-up across the included studies was 34 months, with a range of 3 months to 44 months. Studies with longer follow-up periods are more likely to observe recurrence and a decline in visual acuity. Studies with a shorter period of follow-up cannot comment on the long-term recurrence rates and the need for long-term injections. It is interesting to note that across the studies, the only study noting a significantly worse final BCVA at final follow-up was the study with the longest follow-up time, with a mean follow-up of 44 months or almost 4 years. For this reason, it is difficult to draw definitive conclusions across studies on the rate of recurrence. Further studies with longer follow-up intervals are needed to better understand the long-term outcomes and best management practices for patients with pCNVM. Future research should include patients with pCNVM in randomized controlled trials to evaluate the efficacy of anti-VEGF agents, long-term outcomes, recurrence rates, and quality of life. Finally, the existing literature does not address how pCNVM affects the visual field of affected patients. Given that some of these membranes wrap around the optic nerve, they may impact vision in ways beyond central acuity, potentially influencing peripheral vision or other aspects of the visual field. Further research is needed to explore these visual field changes and their implications for patient outcomes. Conclusion Overall, the literature supports the use of intravitreal anti-VEGF injections for the management of pCNVM of all etiologies. The existing evidence, with an overall low risk of bias, suggests that a conservative PRN treatment strategy with as few as one injection may improve visual acuity in the short term, and may be the most reasonable treatment strategy in this unique group of patients. References Ruben S, Palmer H, Marsh RJ. The visual outcome of peripapillary choroidal neovascular membranes. Acta Ophthalmol (Copenh). 1994;72(1):118-21. D'souza P, Ranjan R, Babu U, Kanakath AV, Saravanan VR. 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Supplementary Material Supplementary material 1 is not available with this version Additional Declarations There is no conflict of interest Supplementary Files SupplementalMaterial.docx Cite Share Download PDF Status: Published Journal Publication published 26 Oct, 2025 Read the published version in Eye → Version 1 posted Editorial decision: revise 12 May, 2025 Review # 1 received at journal 02 May, 2025 Reviewer # 1 agreed at journal 02 May, 2025 Reviewers invited by journal 07 Jan, 2025 Editor assigned by journal 20 Dec, 2024 Submission checks completed at journal 16 Dec, 2024 First submitted to journal 14 Dec, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5645654","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":398854136,"identity":"8353419d-3825-456b-92ac-62d1c40e83b9","order_by":0,"name":"Rahul Sharma","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABA0lEQVRIiWNgGAWjYFACHgaGBzAGEMiBiAMPCGlJQNJiDNaSQIqWxAYQiU+LefvZYxIJNXX2/P1nD36uzLFLnx92+CHQFjs53QbsWmTO5KVJJBw7nDjjRl6y5Nltybkbb6cZALUkG5sdwK5FgiHHTCKBDajmBo+BZOM25tyNsxNAWg4kbsOlhf8NUMu/Onv582eMfzZuq083nJ3+Ab8WCaAtiW3MjBsO5JgBbTmcIC+dQ8AWiTfGFol9hxM33sgxs2zcdtxwg3ROwYEEAzx+4c8xvPHhW529HNBhNxu3VcvLz07f/OFDhZ0cLi2YwACs0oBY5SAg30CK6lEwCkbBKBgJAACnMGICr+UMEQAAAABJRU5ErkJggg==","orcid":"","institution":"University of Toronto","correspondingAuthor":true,"prefix":"","firstName":"Rahul","middleName":"","lastName":"Sharma","suffix":""},{"id":398854137,"identity":"edc751ea-91be-49ae-97df-496ee8a9e231","order_by":1,"name":"Angelica Hanna","email":"","orcid":"https://orcid.org/0009-0001-6233-9806","institution":"University of Toronto","correspondingAuthor":false,"prefix":"","firstName":"Angelica","middleName":"","lastName":"Hanna","suffix":""},{"id":398854138,"identity":"561a17d3-8920-4267-8da5-90dfa92146c4","order_by":2,"name":"Aswen Sriranganathan","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Aswen","middleName":"","lastName":"Sriranganathan","suffix":""},{"id":398854139,"identity":"62223053-3ef3-412b-bd85-4c481f3dc6a5","order_by":3,"name":"Peter Kertes","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Kertes","suffix":""},{"id":398854140,"identity":"288480a7-c31c-4f40-937c-7317574356ac","order_by":4,"name":"Gary Yau","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Gary","middleName":"","lastName":"Yau","suffix":""}],"badges":[],"createdAt":"2024-12-15 03:10:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5645654/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5645654/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41433-025-04080-x","type":"published","date":"2025-10-26T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":73517903,"identity":"546ac052-4a04-46cc-b7f3-59bfd150a280","added_by":"auto","created_at":"2025-01-10 17:59:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":140698,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA flow diagram outlining the study selection process\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5645654/v1/8611db3bde5f97d7453fb38c.png"},{"id":94443631,"identity":"e9a39082-4be0-41a7-9efe-1194669d8854","added_by":"auto","created_at":"2025-10-27 14:30:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":756274,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5645654/v1/cbe843d0-5f30-4063-a31a-aa3a6f7ed4c8.pdf"},{"id":73517921,"identity":"019482bc-a822-41d1-a799-d48870e3f1f5","added_by":"auto","created_at":"2025-01-10 17:59:12","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":43072,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalMaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-5645654/v1/e277b08143dfe82a67986aef.docx"}],"financialInterests":"There is no conflict of interest","formattedTitle":"Anti-Vascular Endothelial Growth Factor for the Management of Peripapillary Choroidal Neovascular Membrane: A Systematic Review","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePeripapillary choroidal neovascular membrane (pCNVM) is an uncommon subtype of choroidal neovascularization, representing approximately 10% of all cases.(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) pCNVM are seen in a variety of underlying diagnoses: degenerative conditions (AMD, angioid streaks, and pathological myopia); inflammatory pathologies (chronic uveitis, including Vogt\u0026ndash;Koyanagi\u0026ndash;Harada syndrome (VKH), ocular tuberculosis, and toxoplasmosis); optic nerve disorders (papilledema, tilted optic disc syndrome, optic nerve drusen); neoplastic disorders (choroidal naevi, osteoma); vascular disorders (polypoidal choroidal vasculopathy).(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) For between 17 and 39% of cases, however, the exact cause of pCNVM remains unidentified, leading to the classification of these cases as idiopathic.(\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Compared to other locations of CNVM, pCNVM is more likely to be idiopathic.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eFurthermore, compared to neovascularization at other locations, the visual significance of pCNVM varies. As many as two-thirds of cases of pCNVM remain asymptomatic, with the membrane restricted to the extrafoveal location.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) Patients may, however, present with significant visual disturbances due to the extension of the membrane to the fovea or due to the presence of subretinal fluid.\u003csup\u003e(5)\u003c/sup\u003e pCNVM may mimic disc edema, central serous chorioretinopathy, chronic inflammatory lesions, and optic disc neovascularization associated with ischemic or vascular diseases.\u003c/p\u003e \u003cp\u003eHistorically, the primary treatment options available for pCNVM have included surgery, laser photocoagulation, photodynamic therapy, and intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) For choroidal neovascularization at any location, anti-VEGF therapy is the most commonly used therapeutic modality.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) Compared to macular CNVM, functional visual changes experienced by patients with pCNVM may vary and thus may warrant a different treatment approach.(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) The guidance on pCNVM specifically is limited compared to that for choroidal neovascularization in other locations. The purpose of this systematic review is to outline (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) the visual and anatomical outcomes associated with the use of various anti-VEGF drugs for treatment of pCNVM and (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) the possible treatment regimens used, providing a comprehensive understanding of the effectiveness of each.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eAn electronic search strategy was developed in consultation with an experienced medical information specialist (Supplemental Material 1). We used this strategy to search Ovid MEDLINE, Ovid EMBASE, and CINAHL databases from their January 2000 to December 2024. The study protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO 2024, registration number, CRD42024551949).\u003c/p\u003e \u003cp\u003eAll results were exported to Covidence (Veritas Health Innovation, Melbourne, Australia), where duplicates were removed. For primary study selection, titles and abstracts from the initial search were screened by two independent reviewers (AH and AS) using established eligibility criteria. For secondary study selection, the full texts of selected studies were assessed by two independent reviewers (AH and AS) against the eligibility criteria. An explanation was provided for the excluded full texts. Any disagreement between reviewers regarding the inclusion of a study was resolved through consensus.\u003c/p\u003e \u003cp\u003eThis review included any study that explored the clinical outcomes of patients with pCNVM after intravitreal anti-VEGF injections. Experimental and observational studies were included. Studies had to contain original data, and reviews and editorials were excluded. Patients receiving combined therapy of anti-VEGF injection in conjunction with other therapies such as photodynamic laser, or laser photocoagulation were excluded. Case reports, conference abstracts and non-English studies were excluded. There were no restrictions for the year of publication.\u003c/p\u003e \u003cp\u003eData extraction was conducted using a tool that included key elements listed in Supplemental Material 2. Two independent reviewers (AH and AS) extracted data from studies and discrepancies were resolved through consensus. Descriptive statistics were used to summarize findings.\u003c/p\u003e \u003cp\u003eThe risk of bias (RoB) for case series was assessed using the Joanna Briggs Institute (JBI) critical appraisal tool for case series. The tool addresses the internal validity and risk of bias of case series designs, addressing confounding, selection, and information bias, in addition to the importance of clear reporting.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) The risk of bias (RoB) for cohort studies was assessed using the Newcastle Ottawa RoB assessment scale, which assesses studies in the domains of patient selection, comparability of the cohorts and outcome measures.(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) The selection domain could receive a maximum of four stars, comparability could receive a maximum of two stars, and outcome could receive a maximum of three stars.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePRISMA results\u003c/h2\u003e \u003cp\u003eThe search yielded 274 results. Following deduplication, 193 studies underwent title/abstract screening of which 36 full texts were reviewed. Ultimately, 10 full texts were included in this study. The PRISMA flow diagram is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDemographics\u003c/h3\u003e\n\u003cp\u003eTwo hundred and sixty-nine eyes of 256 patients were included in this review. The mean age of the included participants was 68 years and the cumulative percentage of female patients across the studies was 53% and the percentage male was 47%. The percentage female and the mean age for each study is reported in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003ch3\u003eStudy Designs, Locations, Time Periods and Risk of Bias Assessments\u003c/h3\u003e\n\u003cp\u003eThe included studies took place between 2003 and 2023. Three of the studies were conducted in India and two studies were conducted in Israel. The remaining five studies were conducted in Spain, Germany, the United States, Lebanon, and Switzerland. Nine of the studies were case series and one study was a retrospective cohort study. The RoB assessments are shown in Supplemental Tables\u0026nbsp;2 and 3. Amongst the case series, there was an overall low risk of bias with the mean score being nine out of ten. The retrospective cohort study showed an intermediate risk of bias with a score of six out of nine, given the lack of a control group.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of included studies and patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNumber of eyes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePercentage Female\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean Age\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eEtiology\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eStudy Location\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD'souza 2018\u003csup\u003e(2)\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eInflammatory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFigueroa 2008(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAMD, angioid streaks, idiopathic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSpain\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHoeh 2009\u003csup\u003e10\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" 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2019\u003csup\u003e12\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIIH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSwitzerland\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRabina 2022\u003csup\u003e13\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAMD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIsrael\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRoy 2017\u003csup\u003e14\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eInflammatory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingh 2020\u003csup\u003e15\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIdiopathic, AMD, inflammatory, angioid streaks, IIH, choroidal rupture, optic nerve head drusen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStanescu 2023\u003csup\u003e16\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAMD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIsrael\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eEtiology of pCNVM in Included Patients\u003c/h3\u003e\n\u003cp\u003eAcross the studies, patients with various etiologies of pCNVM were included. Six studies examined a total of 163 eyes with age-related macular degeneration (AMD), while four studies included 56 eyes with pCNVM of inflammatory etiologies. Three studies included 29 eyes of patients with idiopathic pCNVM and two studies included 9 eyes of patients with angioid streaks. One study reported on 6 eyes with idiopathic intracranial hypertension (IIH), and another study documented one eye each with choroidal rupture and optic nerve head drusen.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eAnti-VEGF Drug and Treatment Strategy Used\u003c/h2\u003e \u003cp\u003eTwo hundred and fifteen eyes received bevacizumab, 41 eyes received aflibercept and 22 eyes received ranibizumab. Note that some patients were started on one agent but switched to another. Eight studies used a pro re nata (PRN) strategy, one study used a 3-injection loading phase followed by a PRN phase(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) and one study used a fixed schedule strategy.(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eNumber of Injections Administered and Follow-up Across Studies\u003c/h3\u003e\n\u003cp\u003eAcross the studies, a mean of 7 injections were administered, but the mean number of injections in each study ranged from 2 to 14. In the studies using a PRN treatment strategy, there was a mean of 6 injections given to patients. For the study using the 3-injection loading phase followed by PRN therapy, there was a mean of 7 injections used. For the study using a fixed interval treatment strategy, there was a mean of 3 injections administered. The mean follow-up across studies was 34 months, with a range of 3 months to 44 months.\u003c/p\u003e\n\u003ch3\u003eVisual Acuity Changes\u003c/h3\u003e\n\u003cp\u003eEight of the ten studies reported an improvement in patients\u0026rsquo; visual acuity at final follow-up after treatment, with two studies reported worse visual acuities compared to baseline and final follow-up. Across all studies, the mean logMAR change in visual acuity following treatment was 0.092, or approximately one Snellen line of improvement. The change in visual acuity for each study is reported in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Four of the studies showed a statistically significant improvement in vision after treatment, and one study showed a non-statistically significant improvement in vision. Three studies did not report on the statistical significance of the improved visual acuity.\u003c/p\u003e \u003cp\u003eOne study showed a statistically significant decrease in vision at final follow-up and one study reported a non-statistically significant decrease in vision.\u003c/p\u003e \u003cp\u003eAmong the patients treated with a PRN strategy, the change in visual acuity ranged from a decrease in vision by -0.19 (equivalent to a loss of approximately 2 Snellen lines) to a gain in vision by 0.31 (equivalent to an improvement of approximately 3 Snellen lines) on the logMAR scale. The mean change in visual acuity for those patients treated using a PRN strategy was an improvement of 0.08. In the study where patients were treated with a loading phase followed by a PRN phase(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), there was a decrease in logMAR visual acuity by 0.1. In the study where patients were treated with a regular dose, in which all cases were due to AMD, there was an increase in visual acuity by 0.29.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eChoroidal and Macular Thickness Changes\u003c/h2\u003e \u003cp\u003eTwo of the studies, D\u0026rsquo;Souza 2018 and Singh 2020, measured macular thickness.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) Both studies found a decrease in macular thickness, with a mean decrease in macular thickness of 138.9 \u0026micro;m. Singh 2020 reported that this was a statically significant decrease (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), while D\u0026rsquo;Souza 2018 did not report p values. Singh 2020 measured choroidal thickness(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) and found a non-statistically significant decrease in choroidal thickness after injection, with a mean decrease of 41 \u0026micro;m (p\u0026thinsp;=\u0026thinsp;0.2).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eRecurrence\u003c/h2\u003e \u003cp\u003eAcross the studies, 6 studies reported on the rate of recurrences. Among these studies, 2 studies reported that none of the patients had a recurrence within the study follow-up period (0% recurrence rate). The remaining four studies had a recurrence rate of between 13 and 85%. Across the studies reporting on recurrences, the mean recurrence rate was 54%. The etiologies of the cases that recurred were inflammatory (n\u0026thinsp;=\u0026thinsp;6), AMD (n\u0026thinsp;=\u0026thinsp;12) and angioid streaks (n\u0026thinsp;=\u0026thinsp;1).\u003c/p\u003e \u003cp\u003eAmong the 4 studies reporting that patients had a recurrence, the mean recurrence occurred at 8 months following initial treatment. One study, however, reported that recurrence occurred as early as 3 months or as late as 74 months after initial injection. Only one study commented on visual acuity at recurrence, noting that there was a one line drop in visual acuity upon recurrence. Two studies reported on the mean number of injections required following recurrence, with one study reporting as many as 6 injections required and the other study reporting the need for only one injection after recurrence. Even after recurrence, however, patients generally had an improvement in final visual acuity after a follow up injection (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eComplications\u003c/h2\u003e \u003cp\u003eAcross the studies, there were no reports of adverse events associated with the use of anti-VEGF therapy for the treatment of pCNVM.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u0026ndash; Anti-VEGF drug, treatment strategy, number of doses and visual acuity changes of the included studies\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDrug\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTreatment strategy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean Doses\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean Baseline BCVA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMean Final BCVA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMean Change in BCVA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eP values\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD'souza 2018(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBevacizumab and Ranibizumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eas needed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFigueroa 2008(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBevacizumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eas needed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.375\u0026thinsp;\u0026plusmn;\u0026thinsp;0.222\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.195\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNot reported\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHoeh 2009(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBevacizumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eas needed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNot reported\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLin 2019(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBevacizumab and Aflibercept\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eregular dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.294\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMansour 2008(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBevacizumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eas needed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOzgonul 2019(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBevacizumab, Ranibizumab and Aflibercept\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eas needed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNot reported\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRabina 2022(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBevacizumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLoading phase followed by as-needed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.46\u0026thinsp;\u0026plusmn;\u0026thinsp;0.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e-0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRoy 2017(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBevacizumab and Ranibizumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eas needed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.083\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingh 2020(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBevacizumab, Ranibizumab and Aflibercept\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eas needed\u003c/p\u003e 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needed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e-0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis systematic review has demonstrated that intravitreal anti-VEGF injections are an effective treatment strategy for pCNVM, leading to improvements in visual acuity and macular thickness. Patients with various etiologies of pCNVM, including AMD, inflammatory conditions, idiopathic cases, and others, benefited from anti-VEGF therapy. Although the included studies varied in terms of the specific anti-VEGF agent used, treatment strategy, and follow-up duration, the overall outcomes suggest that anti-VEGF injections are a favorable treatment in the management of pCNVM. From a long-term visual acuity perspective, conservative treatment strategies, like a PRN approach, are successful in the management of this disease.\u003c/p\u003e \u003cp\u003eAnti-VEGF therapy appears to be an effective therapy for the management of pCNVM of many etiologies and is the most commonly used treatment strategy, however, other therapeutic modalities exist. Surgery has historically been used, but the advent of less invasive treatments has significantly reduced its role in management.(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) Photodynamic therapy, is another treatment that has been used for the treatment of CNVM, however it cannot be done over the nerve and may cause visual disturbances following treatment.(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) Laser photocoagulation is another treatment option for the treatment of extrafoveal choroidal neovascularization and has shown long-term benefits in visual acuity, however, is not as commonly used as anti-VEGF therapy due to potential decreases in vision in the short term .(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe majority of the included studies reported an improvement in visual acuity following anti-VEGF therapy. There was mean improvement of one Snellen line across all studies was 0.092, indicating an overall modest visual gain. Additionally, studies measuring macular thickness found a statistically significant reduction, suggesting that anti-VEGF therapy not only improves visual function but also has a beneficial effect on the structural characteristics of the retina. Despite the variability in treatment strategies\u0026mdash;including pro re nata (PRN), loading doses followed by PRN, and fixed schedules\u0026mdash;most patients showed improved outcomes.\u003c/p\u003e \u003cp\u003eThe variability in treatment regimens reflects the lack of a standardized approach to managing pCNVM. While some studies used a PRN strategy, administering injections only when needed, others employed a fixed regimen, or a loading phase followed by PRN treatment. The mean number of injections varied, with a range from 2 to 14 across different studies, highlighting the need for a tailored approach based on individual patient responses and the etiology of pCNVM. Importantly, this review found that anti-VEGF therapy was generally safe, with no serious complications reported across the included studies. It is also interesting to note that conservative treatment strategies, such as a PRN approach, ultimately resulted in good final visual acuity despite possible short-term decreases in vision upon membrane recurrence between doses.\u003c/p\u003e \u003cp\u003eThis review included the treatment of many disease etiologies. Interestingly, approximately 40% of pCNVM cases are idiopathic.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Only three of the ten studies included in this review addressed this important subgroup of patients.. Given the most common etiologies of pCNVM, it is important to rule out degenerative pathology, inflammatory causes, vascular causes, optic nerve disorders, and neoplastic disorders before concluding that a case of pCNVM is idiopathic. The limited evidence from the three studies including idiopathic cases (involving 29 eyes), showed that anti-VEGF injections were effective for the management of idiopathic pCNVM with improvements in visual acuity. Only one study reported on the structural changes in idiopathic patients noting no changes in the macular or choroidal thickness following anti-VEGF injections.(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eA limitation of this review is the lack of experimental trials. Of the ten included studies, nine studies were case series. Although these case series were of high quality, none of the existing evidence compares treatments in a prospective and standardized manner through comparative studies. Furthermore, the variability in treatment strategies, follow-up durations, and patient populations across the studies introduces heterogeneity, complicating direct comparisons and the establishment of a standardized treatment protocol for pCNVM.\u003c/p\u003e \u003cp\u003eFurthermore, an inherit limitation of the systematic review is the heterogeneity of studies, with studies originating from a diverse group of countries and settings. However, this heterogeneity can also enhance the generalizability of findings, as the consistent trend of treatment efficacy across varied populations suggests broader applicability. While a meta-analysis was not feasible due to the heterogeneity in study designs, populations, and outcomes, we employed a narrative synthesis to systematically compare and contrast key differences and similarities across studies, providing a comprehensive understanding of the evidence base.\u003c/p\u003e \u003cp\u003eAnother limitation of this review is the follow-up period of the included studies. The mean duration of follow-up across the included studies was 34 months, with a range of 3 months to 44 months. Studies with longer follow-up periods are more likely to observe recurrence and a decline in visual acuity. Studies with a shorter period of follow-up cannot comment on the long-term recurrence rates and the need for long-term injections. It is interesting to note that across the studies, the only study noting a significantly worse final BCVA at final follow-up was the study with the longest follow-up time, with a mean follow-up of 44 months or almost 4 years. For this reason, it is difficult to draw definitive conclusions across studies on the rate of recurrence. Further studies with longer follow-up intervals are needed to better understand the long-term outcomes and best management practices for patients with pCNVM.\u003c/p\u003e \u003cp\u003eFuture research should include patients with pCNVM in randomized controlled trials to evaluate the efficacy of anti-VEGF agents, long-term outcomes, recurrence rates, and quality of life. Finally, the existing literature does not address how pCNVM affects the visual field of affected patients. Given that some of these membranes wrap around the optic nerve, they may impact vision in ways beyond central acuity, potentially influencing peripheral vision or other aspects of the visual field. Further research is needed to explore these visual field changes and their implications for patient outcomes.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOverall, the literature supports the use of intravitreal anti-VEGF injections for the management of pCNVM of all etiologies. The existing evidence, with an overall low risk of bias, suggests that a conservative PRN treatment strategy with as few as one injection may improve visual acuity in the short term, and may be the most reasonable treatment strategy in this unique group of patients.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRuben S, Palmer H, Marsh RJ. The visual outcome of peripapillary choroidal neovascular membranes. Acta Ophthalmol (Copenh). 1994;72(1):118-21.\u003c/li\u003e\n\u003cli\u003eD\u0026apos;souza P, Ranjan R, Babu U, Kanakath AV, Saravanan VR. INFLAMMATORY CHOROIDAL NEOVASCULAR MEMBRANE: Long-Term Visual and Anatomical Outcomes After Intravitreal Anti\u0026ndash;vascular Endothelial Growth Factor Therapy. RETINA. 2018;38(7):1307-15.\u003c/li\u003e\n\u003cli\u003eJutley G, Tah V, Lindfield D, Menon G. Treating peripapillary choroidal neovascular membranes: a review of the evidence. Eye (Lond). 2011;25(6):675-81.\u003c/li\u003e\n\u003cli\u003eCohen SY, Laroche A, Leguen Y, Soubrane G, Coscas GJ. Etiology of Choroidal Neovascularization in Young Patients. Ophthalmology. 1996/08/01;103(8).\u003c/li\u003e\n\u003cli\u003eBrowning DJ, Fraser CM. Ocular conditions associated with peripapillary subretinal neovascularization, their relative frequencies, and associated outcomes. Ophthalmology. 2005;112(6):1054-61.\u003c/li\u003e\n\u003cli\u003eLopez PF, Green WR. Peripapillary subretinal neovascularization. A review. Retina. 1992;12(2):147-71.\u003c/li\u003e\n\u003cli\u003eWilde C, Poostchi A, Mehta RL, Hillman JG, MacNab HK, Messina M, et al. Prevalence of peripapillary choroidal neovascular membranes (PPCNV) in an elderly UK population\u0026mdash;the Bridlington eye assessment project (BEAP): a cross-sectional study (2002\u0026ndash;2006). Eye. 2018 Oct 12;33(3).\u003c/li\u003e\n\u003cli\u003eLin T, Dans K, Meshi A, Muftuoglu IK, Amador-Patarroyo MJ, Chen KC, et al. Age-Related Macular Degeneration-Associated Peripapillary Choroidal Neovascularization in the Era of Anti-Vascular Endothelial Growth Factor Therapy. Retina. 2019;39(10):1936-44.\u003c/li\u003e\n\u003cli\u003eFigueroa MS, Noval S, Contreras I. Treatment of peripapillary choroidal neovascular membranes with intravitreal bevacizumab. British Journal of Ophthalmology. 2008;92(9):1244.\u003c/li\u003e\n\u003cli\u003eMunn Z, Barker TH, Moola S, Tufanaru C, Stern C, McArthur A, et al. Methodological quality of case series studies: an introduction to the JBI critical appraisal tool. (2689-8381 (Electronic)).\u003c/li\u003e\n\u003cli\u003eWells G, Shea B, O\u0026rsquo;Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Available from: https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.\u003c/li\u003e\n\u003cli\u003eRabina G, Ayalon A, Mimouni M, Stanescu N, Moisseiev E, Nemet AY, et al. Optical Coherence Tomography Prognostic Factors in Age-Related Macular Degeneration Patients with Peripapillary Choroidal Neovascularization. Ophthalmologica. 2021;245(4):342-9.\u003c/li\u003e\n\u003cli\u003eSingh SR, Fung AT, Fraser-Bell S, Lupidi M, Mohan S, Gabrielle P-H, et al. One-year outcomes of anti-vascular endothelial growth factor therapy in peripapillary choroidal neovascularisation. British Journal of Ophthalmology. 2020;104(5):678.\u003c/li\u003e\n\u003cli\u003eHoeh AE, Schaal KB, Ach T, Dithmar S. Treatment of Peripapillary Choroidal Neovascularization with Intravitreal Bevacizumab. European Journal of Ophthalmology. 2009;19(1):163-5.\u003c/li\u003e\n\u003cli\u003eMansour AM, Mackensen F, Arevalo JF, Ziemssen F, Mahendradas P, Mehio-Sibai A, et al. Intravitreal Bevacizumab in Inflammatory Ocular Neovascularization. American Journal of Ophthalmology. 2008;146(3):410-6.e1.\u003c/li\u003e\n\u003cli\u003eOzgonul C, Moinuddin O, Munie M, Lee MS, Bhatti MT, Landau K, et al. Management of Peripapillary Choroidal Neovascular Membrane in Patients With Idiopathic Intracranial Hypertension. Journal of Neuro-Ophthalmology. 2019;39(4).\u003c/li\u003e\n\u003cli\u003eRoy R, Saurabh K, Bansal A, Kumar A, Majumdar AK, Paul SS. Inflammatory choroidal neovascularization in Indian eyes: Etiology, clinical features, and outcomes to anti-vascular endothelial growth factor. Indian Journal of Ophthalmology. 2017;65(4).\u003c/li\u003e\n\u003cli\u003eStanescu N, Friehmann A, Nemet A, Keshet Y, Ohayon A, Greenbaum E, et al. Long-term outcomes of anti-vascular endothelial growth factor treatment in peripapillary choroidal neovascularisation due to age-related macular degeneration. Eye. 2023;37(6):1202-6.\u003c/li\u003e\n\u003cli\u003eAisenbrey S, Gelisken F. Surgical treatment of peripapillary choroidal neovascularisation. The British Journal of Ophthalmology. 2007 Mar 6;91(8).\u003c/li\u003e\n\u003cli\u003eBandello F, Lanzetta P, Battaglia Parodi M, Roman-Pognuz D, Saviano S, Ravalico G. Photodynamic therapy of subfoveal recurrences after laser photocoagulation of extrafoveal choroidal neovascularization in pathologic myopia. Graefes Arch Clin Exp Ophthalmol. 2003;241(7):567-70.\u003c/li\u003e\n\u003cli\u003eNewman DK. Photodynamic therapy: current role in the treatment of chorioretinal conditions. Eye (Lond). 2016;30(2):202-10.\u003c/li\u003e\n\u003cli\u003eBusbee BG, Brown MM, Brown GC, Sharma S. CME review: A cost-utility analysis of laser photocoagulation for extrafoveal choroidal neovascularization. Retina. 2003;23(3):279-87; ; quiz 443-4.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Supplementary Material","content":"\u003cp\u003eSupplementary material 1 is not available with this version\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"eye","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"eye","sideBox":"Learn more about [Eye](http://www.nature.com/eye/)","snPcode":"41433","submissionUrl":"https://mts-eye.nature.com/cgi-bin/main.plex","title":"Eye","twitterHandle":"@eye_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5645654/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5645654/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eTo explore the evidence on the use of anti-vascular endothelial growth factor (anti-VEGF) therapy for the treatment of peripapillary choroidal neovascular membrane (pCNVM).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eMedline, Embase and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched between January 2000 and December 2024 for relevant articles that used anti-VEGF therapy to treat pCNVM of any origin. This review followed PRISMA guidelines and was prospectively registered (PROSPERO registration number CRD42024551949).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTen studies reporting on 269 eyes were included. Eight studies used a pro re nata (PRN) strategy, 1 study used a loading phase followed by an as-needed phase and 1 study used a fixed schedule strategy. There was a mean of 7 injections required. Eight studies reported improvements in best corrected visual acuity (BCVA) at final follow-up following treatment. The mean logarithm of the minimum angle of resolution (logMAR) change was 0.092, or approximately one line Snellen improvement. Two studies reported on macular thickness, and one reported on choroidal thickness after treatment, all of which noted decreased thickness at final follow-up. No significant complications were reported.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eFor patients with pCNVM of various etiologies, anti-VEGF injections using any treatment strategy, including conservative management with a PRN approach, seems to be a safe and effective therapy associated with improved visual acuity.\u003c/p\u003e","manuscriptTitle":"Anti-Vascular Endothelial Growth Factor for the Management of Peripapillary Choroidal Neovascular Membrane: A Systematic Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-10 17:59:06","doi":"10.21203/rs.3.rs-5645654/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2025-05-12T07:45:03+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-05-02T13:48:57+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-05-02T13:13:46+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2025-01-07T11:53:27+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-12-20T12:24:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-12-16T14:19:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"Eye","date":"2024-12-15T03:05:53+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"eye","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"eye","sideBox":"Learn more about [Eye](http://www.nature.com/eye/)","snPcode":"41433","submissionUrl":"https://mts-eye.nature.com/cgi-bin/main.plex","title":"Eye","twitterHandle":"@eye_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"63c3c46b-8997-4474-82b5-afec4e7cf9c6","owner":[],"postedDate":"January 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-27T13:08:06+00:00","versionOfRecord":{"articleIdentity":"rs-5645654","link":"https://doi.org/10.1038/s41433-025-04080-x","journal":{"identity":"eye","isVorOnly":false,"title":"Eye"},"publishedOn":"2025-10-26 04:00:00","publishedOnDateReadable":"October 26th, 2025"},"versionCreatedAt":"2025-01-10 17:59:06","video":"","vorDoi":"10.1038/s41433-025-04080-x","vorDoiUrl":"https://doi.org/10.1038/s41433-025-04080-x","workflowStages":[]},"version":"v1","identity":"rs-5645654","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5645654","identity":"rs-5645654","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}