Impact factor (WEB OF SCIENCE - Clarivate)

2 year: 7.664 | 5 year: 7.127


A systematic review of clinical practice guidelines for myopic macular degeneration

Yanxian Chen1,2, Xiaotong Han2, Iris Gordon3, Sare Safi4, Gareth Lingham5, Jennifer Evans3, Jinying Li1, Mingguang He1,2.6, Stuart Keel7

1 Department of Ophthalmology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
2 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
3 Cochrane Eyes and Vision, International Centre for Eye Health, London School of Hygiene and Tropical Medicine, London, UK
4 Ophthalmic Epidemiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5 Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia
6 Centre for Eye Research Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Australia
7 Vision and Blindness Prevention Programme, World Health Organization, Geneva, Switzerland




Myopic macular degeneration (MMD) is a primary cause of blindness and visual impairment in many parts of the world. A review of clinical practice guidelines (CPGs) for intervention selection are required with the increasing demand for MMD management in clinical practice as well as in national health services. Therefore, we aim to systematically review CPGs for MMD and assist the recommendations development of the Package of Eye Care Interventions (PECI) program of the World Health Organization.


A systematic review of CPGs published on MMD between 2010 and April 2020 was conducted. Guidelines were evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Cochrane systematic reviews were also included when the evidence from included CPGs were inadequate or contradict.


After applying exclusion criteria and conducting the quality appraisal, two CPGs were finally included. The average of the AGREE II ratings for the identified Guidelines were 56 and 63 respectively (7 for each item). To provide further information on interventions for MMD, one Cochrane review on MMD was additionally identified and included in the study. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs were recommended for patients with myopic choroidal neovascularization (mCNV) as first-line therapy to improve vision and reduce central macular thickness, and ranibizumab showed significant effectiveness compared to photodynamic therapy (PDT). PDT was recommended to be performed in those resistant to the treatment by one CPG but lacked of adequate description and support. Data extracted from the Cochrane systematic reviews indicated that anti-VEGF therapy for mCNV had significant effectiveness in improving visual acuity and reducing CMT compared to PDT with moderate to low certainty of evidence. Ranibizumab and bevacizumab were considered as equally effective with moderate certainty.


The outcomes of this review suggest that high quality clinical practice guidelines for MMD management are limited. Intravitreal injection of anti-VEGF agents was recommended as an effective intervention to treat myopic CNV as the first-line treatment, while there was inadequate guidance for the application of PDT in myopic CNV management. The use of other interventions for MMD were not recommended at this time and additional evidence is called for.

Print Friendly, PDF & Email

Myopic macular degeneration (MMD), also known as degenerative myopia or pathological myopia, is an important cause of blindness and visual impairment in many parts of the world, especially in areas with a high prevalence of myopia [1,2]. It is characterized by the presence of staphyloma, lacquer cracks, Fuchs’ spot or chorio-retinal atrophy at the posterior pole. The prevalence of MMD is reported to be 0.9%-3.1% amongst adults aged 30 years and above in Asia,[35] 1.2% in European populations older than 49 years,[6] and can be as high as 12.0% in those aged >70 years.[7] A rapid rise of this age-related condition can be anticipated in the near future when the young population with a much higher rate of high myopia grow older,[811] posing a profound impact on the public health and eye care service.

Various treatment strategies for MMD have been explored in the last few decades, including macular surgical management,[1214] laser photocoagulation for subfoveal or extra-foveal choroidal neoucascularization,[15,16] photodynamic therapy (PDT),[1719] corticosteroid treatment [20,21] and anti-vascular endothelial growth factor (anti-VEGF) therapy.[2226] Though data have shown some of these treatments are promising, such as anti-VEGF agents [27], the cost utility of these treatments have not been consistently estimated for the purpose of guiding decision-making process of countries and national health services. A systematic review to find the priority of intervention selection for MMD will be of great value.

Given the increasing need for eye care, the World Health Organization (WHO) has highlighted the role of eye care in contributing to the Sustainable Development Goals (SDGs), and is developing an evidence-based Package of Eye Care Interventions (PECI). The methodology for the development of the PECI has been previously published.[28] In brief, the PECI aims at providing a systematic identification of evidence-based eye care interventions for pre-defined priority eye conditions based on high quality clinical practice guidelines (CPGs) and, where needed, systematic reviews, to assist the choice of interventions in clinical decision-making and national health services. This paper aims to present the results of a systematic review of CPGs for MMD, including the quality and current state of evidence, as a part of PECI development.


The systematic review of CPGs is following the procedures reported in the methodology paper previously [28]. Exclusion criteria for each stage of screening can be seen in Table 1. The stages in the review are as follows:

Table 1.  Exclusion criteria in the screening process of clinical practice guidelines

CPG – clinical practice guideline

Systematic literature search

A systematic literature search of academic databases (MEDLINE, Embase, CINAHL, Global Health, Global Index Medicus) and guideline databases (as listed in Appendix S1 of the Online Supplementary Document) was carried out by an information specialist from Cochrane Eyes and Vision (CEV). In addition, professional ophthalmology and optometry associations’ websites were searched for relevant guidelines (Appendix S1 on the Online Supplementary Document). We restricted the searches to the last 10 years and to English language. The search strategy for the academic databases can be found in Appendix S2 on the Online Supplementary Document.

Literature screening and quality appraisal

All the titles and abstracts of articles identified from the literature searches were screened independently by two authors (G.L and S.S). Abstrackr, a semi-automated online citation screening program, was utilized where possible [29]. Concerns about the eligibility were discussed with a CEV representative (J.E.) and the WHO representative (S.K). Two authors (Y.C and X.H) conducted full-text screening of the CPGs relevant to MMD independently, and discussed with a third author when there were disagreements.

Two authors (Y.C and X.H) independently evaluate the quality of the included CPGs using “Appraisal of Guidelines for Research and Evaluation” (AGREE II) [30]. Items 4, 7, 8, 10, 12, 13, 15, 22 and 23 in AGREE II (Appendix 3 on the Online Supplementary Document) were specifically selected according to a consensus finding process [31]. A scale of importance from strongly disagree (1 point) to strongly agree (7 point) was used in each item. A difference of more than 2 points for any item between the two authors were discussed between the two authors to reach a consensus, and the representative of WHO or CEV was involved when necessary.

Guideline selection and data extraction

Following evaluation with the AGREE II tool, guidelines were excluded if the average rating of the two authors for items 4, 7, 8, 12 or 22 was less than 3, or the total rating for all 9 items was below 45. Final selection of a maximum of 5 CPGs according to the following criteria: 1) quality 2) publication time and 3) comprehensiveness (ie, applicability to different settings) with the agreement of the whole study group.

Information related to the recommendation, including type of recommendation, dosage, target population, the strength of recommendation and the quality of the evidence supporting the recommendation, were extracted by one author (Y.C or X.H) and re-reviewed by another author. Disagreements were discussed and resolved by the two researchers and a third author (S.K.). The process was repeated for all the Guidelines until agreement on the recommended eye care interventions was reached.

With respect to the published protocol no changes were performed. The quality check and the methodological support for this study have been provided by WHO/CEV.

Search and selection of systematic reviews

When the evidence from included CPGs were inadequate or contradict, Cochrane Systematic Reviews (CSRs) were sought. The Information Specialist for CEV identified CSRs published in the last 10 years by searching the Cochrane library using the term “myopic macular degeneration. The following search limits were defined for the search strategy in the Cochrane library: 1) Content type: Cochrane Reviews, 2) Cochrane Library publication date: last 10 years, 3) Search word variations: Yes. The search was run on 23 July 2020 and retrieved 7 CSRs. The CEV Information Specialist pre-screened the results and forwarded PDFs of two CSRs that were potentially relevant for inclusion in the review.

Two members of the group (Y.C and X.H) independently performed title and abstract screening. Systematic reviews were excluded if they were older than 10 years or the review was not an intervention or diagnostic test accuracy review that was specifically related to the target eye condition. After comparing the decisions of both researchers, only those CSRs where there was agreement between both authors (Y.C and X.H) were included.


After combining all searches from academic and guideline databases and professional association webpages, 3778 CPGs were identified and underwent independent title and abstract screening. A total of 3575 CPGs met the exclusion criteria and 179 were duplicates, leaving a total of 34 CPGs that were considered potentially relevant and were retrieved to undergo full-text screening and quality appraisal. Of the identified 34 guidelines, we excluded 32 Guidelines for the following reasons: 29 because the content was not relevant to MMD after full-text screening [3260], 3 because the absence or presence of possible conflicts of interest was not stated [27,61,62] (Figure 1).

Figure 1.  Flowchart for the results of the screening process. CPG: clinical practice guideline.

After conducting quality appraisal on the remaining CPGs, and checking for quality, publication time and comprehensiveness, we finally included the following guidelines: “Intravitreal injection of anti-vascular endothelial growth factor agents for ocular vascular diseases; Clinical practice guideline”(2018) [63] developed by Homayoun Nikkhah et al., and “Ranibizumab for treating choroidal neovascularisation associated with pathological myopia”(2013) [64] developed by National Institute for Health and Care Excellence (NICE). The total AGREE II ratings for the former guideline were 56, and this figure for NICE guideline were 63, both were above 45 points (Table 2).

Table 2.  The AGREE II rating of the selected guidelines after full-text screening

MMD – myopic macular degeneration

The included CPG developed by Nikkhah et al. recommended intravitreal anti-VEGF drugs for patients with myopic choroidal neovascularization (mCNV) to improve vision and to reduce central macular thickness. Intravitreal bevacizumab was recommended to be the first-line injection for these patients, and photodynamic therapy (PDT) performed in those resistant to the treatment. The evidence for the recommendations came from 1 meta-analysis, 1 RCT and 1 review, and the evidence level was graded as high. The CPG also recommended that highly myopic patients aged less than 50 years should have funduscopy to ensure early detection of MMD. For older patients with risk factors of CNV recurrence (high degrees of myopia and subfoveal CNV, primary extensive CNV, hemorrhage, choroidal thickness reduction etc), periodic examinations are recommended, but the evidence level of this recommendation was low since it was only supported by case series. In the NICE CPG, intravitreal ranibizumab is recommended as an option for mCNV, and concluded that ranibizumab is a treatment with clinical effectiveness for visual impairment caused by mCNV, supported by 3 RCTs. But the long-term improvement (after 3 months) in BCVA brought by ranibizumab is uncertain. The recommendations and quality of evidence are summarized in Table 3.

Table 3.  Recommended eye interventions for myopic macular degeneration and strength of recommendation and quality of evidence in selected clinical practice guidelines

*1: Intravitreal injection of anti-vascular endothelial growth factor agents for ocular vascular diseases; Clinical practice, 2: Ranibizumab for treating choroidal neovascularisation associated with pathological myopia.

†The listed references in the guideline have no information about the use of photodynamic therapy in resistant cases.

To complement the evidence from the CPG, all Cochrane reviews on the topic area were also checked. In total one Cochrane review on MMD was identified, “Anti-vascular endothelial growth factor for choroidal neovascularisation in people with pathological myopia (Review)” (2016) [65]. In the identified anti-VEGF review, anti-VEGF therapy was found to not cause significantly higher risk of systemic serious adverse events or ocular adverse events compared to PDT. Anti-VEGF therapy also showed a higher quality of life in MMD patients supported with moderate-certainty evidence, and was suggested to be significantly effective in improving visual acuity and reducing central macular thickness compared to PDT with moderate to low certainty of evidence (Table 4). Ranibizumab and bevacizumab were considered to be equally effective with moderate certainty.

Table 4.  Summary of interventions for myopic macular degeneration and certainty of evidence from identified Cochrane systemic reviews

BCVA – best corrected visual acuity, CI – confidence interval, PRN – pro re nata, RR – relative risk, CNV – choroidal neovascularization, CI – confidence interval

An overall view of the strength of recommendation and quality of evidence given in each Guideline is reported in Table 4. There are substantial evidence supporting intravitreal injection of anti-VEGF agent as a beneficial treatment of mCNV, and PDT is also recommended though with lower effectiveness. Laser photocoagulation is not strongly recommended since its role in treating non-subfoveal mCNV is yet to be identified.


The current study reviewed CPGs and Cochrane systemic reviews for MMD, with the aim of providing evidence on eye care interventions for MMD to aid in the development of the PECI. A total of 2 CPGs and 1 Cochrane systemic review were included after a standard screening process. Anti-VEGF therapy was recommended to improve the vision in patients with myopic CNV, among which ranibizumab showed greater effectiveness compared with PDT, while PDT was suggested to use in resistant cases with no solid evidence. Overall, current high-quality CPGs and meta-analysis can provide some guidance for the management of myopic CNV, but the types of interventions involved are limited.

In recent years, anti-VEGF agents have been introduced and rapidly become an important therapy in the treatment of ocular vascular diseases, including age-related macular degeneration, diabetic macular edema, retinal vein occlusion and mCNV [2224,6670]. Anti-VEGF therapy is also a strongly recommended intervention for mCNV in the current study with significantly better visual outcome compared to PDT supported by moderate-certainty evidence [65]. Among the available anti-VEGF agents, ranibizumab and bevacizumab are believed to have equal treatment effect and similar long-term outcome for mCNV. The improved vision of mCNV patients after ranibizumab or bevacizumab intraocular injection was reported to be maintained up to 3 to 4 years [25,7173], however the long term effects remain unclear [74]. While the clinical effectiveness of aflibercept for mCNV still needs to be confirmed with further comparisons with other agents and analysis of cost and utility, as well as long-term observation after treatment. Pegaptanib was reported to be effective in the treatment of mCNV in a case-series study and a case report [75,76], but its effectiveness needs evaluating in larger RCTs. Though anti-VEGF therapy is recommended as first-line therapy, it’s still unclear how long these agents can be used out of local and systemic safety concerns, and what should be done when the first treatment fails. Future guidelines should be developed aiming to fill these gaps.

Among the available treatments for mCNV, PDT with verteporfin has a long history as an established and approved treatment and has been shown to achieve satisfying short-term outcome in improving vision of mCNV patients [1719,7781]. However, the long-term visual outcome with PDT is controversial. Some case-series showed improved vision in mCNV patients after PDT that was maintained up to 2 to 3 years [17,8286], while a randomized clinical trial reported that PDT did not have better visual outcomes compared to placebo after 2 years [87]. In addition, standard-fluence PDT may contribute to chorioretinal atrophy in long term [88,89]. In this study, the CPG from Nikkhah et al. recommended PDT to be performed in cases resistant to intravitreal anti-VEGF treatment, but we found no information about this regimen in the references they listed. The recommendation of PDT was more like a presumptive conclusion from the technical committee. It is also worth noticing that the cost of PDT is quite high, which is unfordable in less-developed areas. Therefore, the application of PDT as a major treatment option or an alternative therapy for myopic patients in clinical practice still needs to be validated with further cost and benefit analysis.

Despite the increasing demands for clinical management of MMD and other complications of pathological myopia, this study found few high-quality CPG. The CPG developed by Nikkhah et al provided clinical recommendations for 5 different ocular vascular diseases and evidence levels of each intervention, but presented a lack of details in terms of clinical effectiveness, cost-effectiveness, and technology of implementation. NICE, as a large government agency that develops guidelines, has only one comprehensive CPG for MMD. Though one Cochrane systemic review has been added to the current study, in total only recommendations on, and evidence for, two interventions were identified. The amount of benefit with surgical technology, including submacular surgery or macular translocation for mCNV, corticosteroid injection and combined therapy remains unclear. In an excluded CPG written by Cheung et al, a detailed recommendation of interventions were provided, that anti-VEGF therapy was considered as the first-line treatment with Class I recommendation, vPDT and intravitreal TA+ vPDT were Class IIa recommendation, macular surgery, laser photocoagulation and intravitreal TA + anti-VEGF therapy were Class IIb recommendation [61]. Our main conclusion that anti-VEGF therapy as first choice for mCNV was in consistence with these recommendations, confirming the status of anti-VEGF therapy among mCNV treatments. However, the types of interventions were limited in our review after excluding the CPGs evaluating more interventions, may lead to inadequate guidance on alternative interventions for patients with specific conditions, including multiple foci of mCNV [90], pregnant women [91] or ocular hypertension [92]. Institutes independent from manufacturers are expected to investigate all the available treatment options for MMD in the future to provide comprehensive guidance for MMD treatments.

There are some inherent limitations in this study. Based on the criteria for identifying guidelines to inform the development of the PECI, only two guidelines were included. Though there have been enough evidence supporting ophthalmologists to use anti-VEGF as first-line therapy for mCNV, guidance is still insufficient for those who have contradictions, specific conditions or failure in taking anti-VEGF therapy. Second, MMD is most prevalent in countries where English is not the primary language. Given the language barrier in publications, some guidelines for MMD may have been omitted in the current analysis. Future study with larger searching database are required to provide better-quality data to help establish the best management strategy for MMD. Third, to assure the objectivity of the results, three papers providing assessment on more than one intervention for MMD were excluded due to possible conflicts of interest. The efficacy and utility of alternative treatments could not be assessed adequately.


There are limited clinical practice guidelines for MMD management met the inclusion criteria of PECI development. Based on existing evidence, intravitreal injection of anti-VEGF agents is suggested to be an effective therapy for myopic CNV and should be the first-line treatment. The application of PDT for mCNV in clinical practice is still lack of adequate guidance. The use of other interventions for MMD is not recommended at this time and further solid evidence is called for.

Additional material

Online Supplementary Document

[1] Funding: Dr Yanxian Chen received support from Science and Technology Planning Project of Shenzhen Municipality (JCYJ20210324110000002).

[2] Authorship contributions: SK devised the project. JE and SS, GL assisted with project developing. IG conducted searching and YC and XH conducted screening and data extraction. Y.C wrote the manuscript. MH, JL and SK reviewed and revised the manuscript.

[3] Competing interests: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author), and declare no conflicts of interest.


[1] A Iwase, M Araie, A Tomidokoro, T Yamamoto, H Shimizu, and Y Kitazawa. Prevalence and Causes of Low Vision and Blindness in a Japanese Adult Population: The Tajimi Study. Ophthalmology. 2006;113:1354-62. DOI: 10.1016/j.ophtha.2006.04.022. [PMID:16877074]

[2] . Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study. Lancet Glob Health. 2021;9:e144-60. DOI: 10.1016/S2214-109X(20)30489-7. [PMID:33275949]

[3] HH Liu, L Xu, YX Wang, S Wang, QS You, and JB Jonas. Prevalence and Progression of Myopic Retinopathy in Chinese Adults: The Beijing Eye Study. Ophthalmology. 2010;117:1763-8. DOI: 10.1016/j.ophtha.2010.01.020. [PMID:20447693]

[4] LQ Gao, W Liu, and Y Liang. Prevalence and characteristics of myopic retinopathy in a rural chinese adult population: The handan eye study. Arch Ophthalmol. 2011;129:1199-204. DOI: 10.1001/archophthalmol.2011.230. [PMID:21911668]

[5] T Asakuma, M Yasuda, T Ninomiya, Y Noda, S Arakawa, and S Hashimoto. Prevalence and risk factors for myopic retinopathy in a Japanese population: the Hisayama Study. Ophthalmology. 2012;119:1760-5. DOI: 10.1016/j.ophtha.2012.02.034. [PMID:22578442]

[6] J Vongphanit, P Mitchell, and JJ Wang. Prevalence and progression of myopic retinopathy in an older population. Ophthalmology. 2002;109:704-11. DOI: 10.1016/S0161-6420(01)01024-7. [PMID:11927427]

[7] Y-L Wong, C Sabanayagam, Y Ding, C-W Wong, AC-H Yeo, and Y-B Cheung. Prevalence, Risk Factors, and Impact of Myopic Macular Degeneration on Visual Impairment and Functioning Among Adults in Singapore. Invest Ophthalmol Vis Sci. 2018;59:4603-13. DOI: 10.1167/iovs.18-24032. [PMID:30242361]

[8] SK Jung, JH Lee, H Kakizaki, and D Jee. Prevalence of myopia and its association with body stature and educational level in 19-year-old male conscripts in seoul, South Korea. Invest Ophthalmol Vis Sci. 2012;53:5579-83. DOI: 10.1167/iovs.12-10106. [PMID:22836765]

[9] J Sun, J Zhou, P Zhao, J Lian, H Zhu, and Y Zhou. High prevalence of myopia and high myopia in 5060 Chinese university students in Shanghai. Invest Ophthalmol Vis Sci. 2012;53:7504-9. DOI: 10.1167/iovs.11-8343. [PMID:23060137]

[10] V Koh, A Yang, SM Saw, YH Chan, ST Lin, and MMH Tan. Differences in prevalence of refractive errors in young Asian males in Singapore between 1996–1997 and 2009–2010. Ophthalmic Epidemiol. 2014;21:247-55. DOI: 10.3109/09286586.2014.928824. [PMID:24990474]

[11] LL Lin, YF Shih, CK Hsiao, and CJ Chen. Prevalence of myopia in Taiwanese schoolchildren: 1983 to 2000. Ann Acad Med Singap. 2004;33:27-33. [PMID:15008558]

[12] JM Ruiz-Moreno and C de la Vega. Surgical removal of subfoveal choroidal neovascularisation in highly myopic patients. Br J Ophthalmol. 2001;85:1041-3. DOI: 10.1136/bjo.85.9.1041. [PMID:11520751]

[13] N Hamelin, A Glacet-Bernard, C Brindeau, G Mimoun, G Coscas, and G Soubrane. Surgical treatment of subfoveal neovascularization in myopia: macular translocation vs surgical removal. Am J Ophthalmol. 2002;133:530-6. DOI: 10.1016/S0002-9394(02)01335-1. [PMID:11931787]

[14] JP Ehlers, R Maldonado, N Sarin, and CA Toth. Treatment of non-age-related macular degeneration submacular diseases with macular translocation surgery. Retina. 2011;31:1337-46. DOI: 10.1097/IAE.0b013e31820668cf. [PMID:21487342]

[15] A Pece, R Brancato, P Avanza, F Camesasca, and L Galli. Laser photocoagulation of choroidal neovascularization in pathologic myopia: long-term results. Int Ophthalmol. 1994-1995;18:339-44. DOI: 10.1007/BF00930311. [PMID:7543889]

[16] JM Ruiz-Moreno and JA Montero. Long-term visual acuity after argon green laser photocoagulation of juxtafoveal choroidal neovascularization in highly myopic eyes. Eur J Ophthalmol. 2002;12:117-22. DOI: 10.1177/112067210201200207. [PMID:12022283]

[17] A Pece, V Isola, M Vadalà, and D Matranga. Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization secondary to pathologic myopia: long-term study. Retina. 2006;26:746-51. DOI: 10.1097/01.iae.0000244256.60524.c0. [PMID:16963846]

[18] JA Montero and JM Ruiz-Moreno. Verteporfin photodynamic therapy in highly myopic subfoveal choroidal neovascularisation. Br J Ophthalmol. 2003;87:173-6. DOI: 10.1136/bjo.87.2.173. [PMID:12543746]

[19] . Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin. Ophthalmology. 2001;108:841-52. DOI: 10.1016/S0161-6420(01)00544-9. [PMID:11320011]

[20] NM Holekamp, MA Thomas, and A Pearson. The safety profile of long-term, high-dose intraocular corticosteroid delivery. Am J Ophthalmol. 2005;139:421-8. DOI: 10.1016/j.ajo.2004.10.005. [PMID:15767049]

[21] WM Chan, TY Lai, AL Wong, DT Liu, and DS Lam. Combined photodynamic therapy and intravitreal triamcinolone injection for the treatment of choroidal neovascularisation secondary to pathological myopia: a pilot study. Br J Ophthalmol. 2007;91:174-9. DOI: 10.1136/bjo.2006.103606. [PMID:16987898]

[22] S Rofagha, RB Bhisitkul, DS Boyer, SR Sadda, and K Zhang. Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). Ophthalmology. 2013;120:2292-9. DOI: 10.1016/j.ophtha.2013.03.046. [PMID:23642856]

[23] A Tufail, PJ Patel, S Sivaprasad, W Amoaku, AC Browning, and M Cole. Ranibizumab for the treatment of choroidal neovascularisation secondary to pathological myopia: interim analysis of the REPAIR study. Eye (Lond). 2013;27:709-15. DOI: 10.1038/eye.2013.8. [PMID:23449508]

[24] S Wolf, VJ Balciuniene, G Laganovska, U Menchini, K Ohno-Matsui, and T Sharma. RADIANCE: a randomized controlled study of ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia. Ophthalmology. 2014;121:682-92.e2. DOI: 10.1016/j.ophtha.2013.10.023. [PMID:24326106]

[25] JM Ruiz-Moreno, L Arias, JA Montero, A Carneiro, and R Silva. Intravitreal anti-VEGF therapy for choroidal neovascularisation secondary to pathological myopia: 4-year outcome. Br J Ophthalmol. 2013;97:1447-50. DOI: 10.1136/bjophthalmol-2012-302973. [PMID:24026146]

[26] Y Ikuno, K Ohno-Matsui, TY Wong, JF Korobelnik, R Vitti, and T Li. Intravitreal Aflibercept Injection in Patients with Myopic Choroidal Neovascularization: The MYRROR Study. Ophthalmology. 2015;122:1220-7. DOI: 10.1016/j.ophtha.2015.01.025. [PMID:25745875]

[27] K Ohno-Matsui, Y Ikuno, TYY Lai, and CM Gemmy Cheung. Diagnosis and treatment guideline for myopic choroidal neovascularization due to pathologic myopia. Prog Retin Eye Res. 2018;63:92-106. DOI: 10.1016/j.preteyeres.2017.10.005. [PMID:29111299]

[28] S Keel, JR Evans, S Block, R Bourne, M Calonge, and CY Cheng. Strengthening the integration of eye care into the health system: methodology for the development of the WHO package of eye care interventions. BMJ Open Ophthalmol. 2020;5:e000533. DOI: 10.1136/bmjophth-2020-000533. [PMID:32821853]

[29] Wallace BC, Small K, Brodley CE, Lau J, Trikalinos TA. Deploying an interactive machine learning system in an evidence-based practice center: abstrackr. Proceedings of the 2nd ACM SIGHIT International Health Informatics Symposium. Miami, Florida, USA: Association for Computing Machinery; 2012.

[30] W Hoffmann-Eßer, U Siering, EAM Neugebauer, AC Brockhaus, N McGauran, and M Eikermann. Guideline appraisal with AGREE II: online survey of the potential influence of AGREE II items on overall assessment of guideline quality and recommendation for use. BMC Health Serv Res. 2018;18:143 DOI: 10.1186/s12913-018-2954-8. [PMID:29482555]

[31] A Rauch, S Negrini, and A Cieza. Toward strengthening rehabilitation in health systems: methods used to develop a WHO package of rehabilitation interventions. Arch Phys Med Rehabil. 2019;100:2205-11. DOI: 10.1016/j.apmr.2019.06.002. [PMID:31207218]

[32] The Royal College of Ophthalmologists. Primary Eye Care Community Ophthalmology and General Ophthalmology. 2019.

[33] KY Lian, G Napper, FJ Stapleton, and PM Kiely. Infection control guidelines for optometrists 2016. Clin Exp Optom. 2017;100:341-56. DOI: 10.1111/cxo.12544. [PMID:28597930]

[34] National Institute for Health and Care Excellence. Ranibizumab; The clinician’s guide to commencing, continuing, and discontinuing treatment. 2009.

[35] A Grzybowski, R Told, S Sacu, F Bandello, E Moisseiev, and A Loewenstein. 2018 Update on Intravitreal Injections: Euretina Expert Consensus Recommendations. Ophthalmologica. 2018;239:181-93. DOI: 10.1159/000486145. [PMID:29393226]

[36] SP Donahue and JB Ruben. US Preventive Services Task Force vision screening recommendations. Pediatrics. 2011;127:569-70. DOI: 10.1542/peds.2011-0020. [PMID:21282266]

[37] KB Freund, JF Korobelnik, R Devenyi, C Framme, J Galic, and E Herbert. Treat-and-extend regimens with anti-vegf agents in retinal diseases: A Literature Review and Consensus Recommendations. Retina. 2015;35:1489-506. DOI: 10.1097/IAE.0000000000000627. [PMID:26076215]

[38] The American Optometric Association. Comprehensive adult eye and vision examination. 2015.

[39] American Academy of Ophthalmology. Comprehensive Adult Medical Eye Evaluation PPP. 2015.

[40] National Institute for Health and Care Excellence. NICE Aflibercept for treating visual impairment caused by macular oedema secondary to central retinal vein occulsion. 2014.

[41] National Institute for Health and Care Excellence. Ranibizumab for treating VI caused by macular oedema. 2013.

[42] AL Siu, K Bibbins-Domingo, DC Grossman, LC Baumann, KW Davidson, and M Ebell. Screening for Impaired Visual Acuity in Older Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2016;315:908-14. DOI: 10.1001/jama.2016.0763. [PMID:26934260]

[43] Royal College of Anaesthetists and Royal College of Ophthalmologists. Local Anaesthesia in Ophthalmic Surgery 2012. 2012.

[44] The Royal Australian and New Zealand College of Ophthalmologists. Guidelines for Performing Intravitreal Therapy. 2017.

[45] The Royal College of Ophthalmologists. Intravitreal Injection Therapy. 2018.

[46] The Royal College of Ophthalmologists. Ophthalmic Imaging. 2019.

[47] BJ Wilson, S Courage, M Bacchus, JA Dickinson, S Klarenbach, and A Jaramillo Garcia. Screening for impaired vision in community-dwelling adults aged 65 years and older in primary care settings. CMAJ. 2018;190:E588-E94. DOI: 10.1503/cmaj.171430. [PMID:29759965]

[48] The Royal College of Ophthalmologists. Theatre facilities and equipment. 2018.

[49] The Royal College of Ophthalmologists. Theatre Procedures. 2018.

[50] The Welsh Government for the NHS Wales. Eye Health Examinations Wales (EHEW); manual and protocols (WHC 2014 007 14). 2014.

[51] The Royal College of Ophthalmologists. Prevention of transmission of blood-borne viruses in ophthalmic surgery. 2010.

[52] National Institute for Health and Care Excellence. Eye conditions. 2019.

[53] WM Gindala and K Lewis. Management of common eye conditions in a primary health care setting; a guide for South Sudan health workers. South Sudan Med J. 2017;10:17-22.

[54] The Royal College of Ophthalmologists. Managing an outbreak of postoperative endophthalmitis. 2016.

[55] The Clinical Council for Eye Health Commissioning (CCEHC). Strategy 2016 – 2018 – Commissioning for the needs of the patients ; enhancing eye health services.

[56] The Royal Australian and New Zealand College of Ophthalmologists. Fluorescein and Indocyanine Green Angiography Guidelines. 2015.

[57] The Royal Australian and New Zealand College of Ophthalmologists. Infection Control in Surgery – Hepatitis B Hepatitis C and HIV (1). 2019.

[58] The Royal Australian and New Zealand College of Ophthalmologists. RANZCO Laser Safety Protocol. 2015.

[59] P Lanzetta and A Loewenstein. Fundamental principles of an anti-VEGF treatment regimen: optimal application of intravitreal anti-vascular endothelial growth factor therapy of macular diseases. Graefes Arch Clin Exp Ophthalmol. 2017;255:1259-73. DOI: 10.1007/s00417-017-3647-4. [PMID:28527040]

[60] The Royal Australian and New Zealand College of Ophthalmologists. Ocular Surgery Guidelines for Ensuring Correct Patient, Correct Eye, Correct Site and Correct Procedure. 2019.

[61] CMG Cheung, JJ Arnold, FG Holz, KH Park, TYY Lai, and M Larsen. Myopic Choroidal Neovascularization: Review, Guidance, and Consensus Statement on Management. Ophthalmology. 2017;124:1690-711. DOI: 10.1016/j.ophtha.2017.04.028. [PMID:28655539]

[62] A Koh, TH Lim, KG Au Eong, C Chee, SG Ong, and N Tan. Optimising the management of choroidal neovascularisation in Asian patients: consensus on treatment recommendations for anti-VEGF therapy. Singapore Med J. 2011;52:232-40. [PMID:21552782]

[63] H Nikkhah, S Karimi, H Ahmadieh, M Azarmina, M Abrishami, and H Ahoor. Intravitreal Injection of Anti-vascular Endothelial Growth Factor Agents for Ocular Vascular Diseases: Clinical Practice Guideline. J Ophthalmic Vis Res. 2018;13:158-69. DOI: 10.4103/jovr.jovr_50_18. [PMID:29719645]

[64] National Institute for Health and Care Excellence. Ranibizumab for treating choroidal neovascularisation associated with pathological myopia. 2013.

[65] Y Zhu, T Zhang, G Xu, and L Peng. Anti-vascular endothelial growth factor for choroidal neovascularisation in people with pathological myopia. Cochrane Database Syst Rev. 2016;12:CD011160. DOI: 10.1002/14651858.CD011160.pub2. [PMID:27977064]

[66] GD Yancopoulos. Clinical application of therapies targeting VEGF. Cell. 2010;143:13-6. DOI: 10.1016/j.cell.2010.09.028. [PMID:20887885]

[67] MC Peden, IJ Suñer, ME Hammer, and WS Grizzard. Long-term outcomes in eyes receiving fixed-interval dosing of anti-vascular endothelial growth factor agents for wet age-related macular degeneration. Ophthalmology. 2015;122:803-8. DOI: 10.1016/j.ophtha.2014.11.018. [PMID:25596618]

[68] JF Korobelnik, DV Do, U Schmidt-Erfurth, DS Boyer, FG Holz, and JS Heier. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014;121:2247-54. DOI: 10.1016/j.ophtha.2014.05.006. [PMID:25012934]

[69] DM Brown, PA Campochiaro, RP Singh, Z Li, S Gray, and N Saroj. Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010;117:1124-33.e1. DOI: 10.1016/j.ophtha.2010.02.022. [PMID:20381871]

[70] A Tufail, N Narendran, PJ Patel, S Sivaprasad, W Amoaku, and AC Browning. Ranibizumab in myopic choroidal neovascularization: the 12-month results from the REPAIR study. Ophthalmology. 2013;120:1944-5.e1. DOI: 10.1016/j.ophtha.2013.06.010. [PMID:24001532]

[71] C Calvo-Gonzalez, J Reche-Frutos, J Donate, C Fernandez-Perez, and J Garcia-Feijoo. Intravitreal ranibizumab for myopic choroidal neovascularization: factors predictive of visual outcome and need for retreatment. Am J Ophthalmol. 2011;151:529-34. DOI: 10.1016/j.ajo.2010.09.021. [PMID:21236413]

[72] N Franqueira, ML Cachulo, I Pires, P Fonseca, I Marques, and J Figueira. Long-term follow-up of myopic choroidal neovascularization treated with ranibizumab. Ophthalmologica. 2012;227:39-44. DOI: 10.1159/000333213. [PMID:22056757]

[73] M Vadalà, A Pece, S Cipolla, C Monteleone, G Fasolino, and A Casuccio. Is ranibizumab effective in stopping the loss of vision for choroidal neovascularisation in pathologic myopia? A long-term follow-up study. Br J Ophthalmol. 2011;95:657-61. DOI: 10.1136/bjo.2009.174243. [PMID:20935305]

[74] V Sarao, D Veritti, S Macor, and P Lanzetta. Intravitreal bevacizumab for choroidal neovascularization due to pathologic myopia: long-term outcomes. Graefes Arch Clin Exp Ophthalmol. 2016;254:445-54. DOI: 10.1007/s00417-015-3076-1. [PMID:26084446]

[75] M Rinaldi, F Chiosi, R DellʼOmo, MR Romano, F Parmeggiani, and F Semeraro. Intravitreal pegaptanib sodium (Macugen) for treatment of myopic choroidal neovascularization: a morphologic and functional study. Retina. 2013;33:397-402. DOI: 10.1097/IAE.0b013e318261a73c. [PMID:22990315]

[76] MD Bennett and W Yee. Pegaptanib for myopic choroidal neovascularization in a young patient. Graefes Arch Clin Exp Ophthalmol. 2007;245:903-5. DOI: 10.1007/s00417-006-0472-6. [PMID:17115175]

[77] T Altan, N Acar, Z Kapran, YB Unver, and S Ozdogan. Outcome of photodynamic therapy in choroidal neovascularization due to pathologic myopia and related factors. Int Ophthalmol. 2012;32:119-25. DOI: 10.1007/s10792-012-9532-6. [PMID:22350116]

[78] JA Montero and JM Ruiz-Moreno. Combined photodynamic therapy and intravitreal triamcinolone injection for the treatment of choroidal neovascularisation secondary to pathological myopia: a pilot study. Br J Ophthalmol. 2007;91:131-3. DOI: 10.1136/bjo.2006.106526. [PMID:17244656]

[79] YS Chen, JY Lin, SY Tseng, SG Yow, WJ Hsu, and SC Tsai. photodynamic therapy for Taiwanese patients with pathologic myopia: a 2-year follow-up. Retina. 2007;27:839-45. DOI: 10.1097/IAE.0b013e31804b1e6f. [PMID:17891006]

[80] K Hayashi, K Ohno-Matsui, S Teramukai, N Shimada, M Moriyama, and W Hara. Photodynamic therapy with verteporfin for choroidal neovascularization of pathologic myopia in Japanese patients: comparison with nontreated controls. Am J Ophthalmol. 2008;145:518-26. DOI: 10.1016/j.ajo.2007.10.032. [PMID:18207125]

[81] DS Lam, WM Chan, DT Liu, DS Fan, WW Lai, and KK Chong. Photodynamic therapy with verteporfin for subfoveal choroidal neovascularisation of pathologic myopia in Chinese eyes: a prospective series of 1 and 2 year follow up. Br J Ophthalmol. 2004;88:1315-9. DOI: 10.1136/bjo.2004.041624. [PMID:15377558]

[82] K Hayashi, K Ohno-Matsui, N Shimada, M Moriyama, W Hayashi, and J Wang. Long-term results of photodynamic therapy for choroidal neovascularization in Japanese patients with pathologic myopia. Am J Ophthalmol. 2011;151:137-47.e1. DOI: 10.1016/j.ajo.2010.06.046. [PMID:20970774]

[83] A Pece, M Vadalà, V Isola, and D Matranga. Photodynamic therapy with verteporfin for juxtafoveal choroidal neovascularization in pathologic myopia: a long-term follow-up study. Am J Ophthalmol. 2007;143:449-54. DOI: 10.1016/j.ajo.2006.11.037. [PMID:17317390]

[84] AM Coutinho, RM Silva, SG Nunes, ML Cachulo, JP Figueira, and JN Murta. Photodynamic therapy in highly myopic eyes with choroidal neovascularization: 5 years of follow-up. Retina. 2011;31:1089-94. DOI: 10.1097/IAE.0b013e3181ff9546. [PMID:21358463]

[85] F Giansanti, G Virgili, MC Donati, M Giuntoli, G Pieretti, and G Abbruzzese. Long-term results of photodynamic therapy for subfoveal choroidal neovascularization with pathologic myopia. Retina. 2012;32:1547-52. DOI: 10.1097/IAE.0b013e3182411cee. [PMID:22481476]

[86] UE Schnurrbusch, C Jochmann, P Wiedemann, and S Wolf. Quantitative assessment of the long-term effect of photodynamic therapy in patients with pathologic myopia. Graefes Arch Clin Exp Ophthalmol. 2005;243:829-33. DOI: 10.1007/s00417-005-1147-4. [PMID:16133036]

[87] KJ Blinder, MS Blumenkranz, NM Bressler, SB Bressler, G Donato, and H Lewis. Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia: 2-year results of a randomized clinical trial–VIP report no. 3. Ophthalmology. 2003;110:667-73. DOI: 10.1016/S0161-6420(02)01998-X. [PMID:12689884]

[88] P Rishi, E Rishi, M Bhende, V Agarwal, CH Vyas, and M Valiveti. Comparison of photodynamic therapy, ranibizumab/bevacizumab or combination in the treatment of myopic choroidal neovascularisation: a 9-year-study from a single centre. Br J Ophthalmol. 2016;100:1337-40. DOI: 10.1136/bjophthalmol-2015-307802. [PMID:26792945]

[89] L Postelmans, B Pasteels, P Coquelet, H El Ouardighi, C Verougstraete, and U Schmidt-Erfurth. Severe pigment epithelial alterations in the treatment area following photodynamic therapy for classic choroidal neovascularization in young females. Am J Ophthalmol. 2004;138:803-8. DOI: 10.1016/j.ajo.2004.06.033. [PMID:15531316]

[90] P Lanzetta, MB Parodi, M Ambesi-Impiombato, G Ravalico, and F Bandello. Early neovascular bridging after photodynamic therapy of myopic choroidal neovascularization. Graefes Arch Clin Exp Ophthalmol. 2004;242:840-4. DOI: 10.1007/s00417-004-0904-0. [PMID:15221306]

[91] TY Wong, K Ohno-Matsui, N Leveziel, FG Holz, TY Lai, and HG Yu. Myopic choroidal neovascularisation: current concepts and update on clinical management. Br J Ophthalmol. 2015;99:289-96. DOI: 10.1136/bjophthalmol-2014-305131. [PMID:24990871]

[92] J Marticorena, F Gomez-Ulla, M Fernandez, B Pazos, MJ Rodriguez-Cid, and M Sanchez-Salorio. Combined photodynamic therapy and intravitreal triamcinolone acetonide for the treatment of myopic subfoveal choroidal neovascularization. Am J Ophthalmol. 2006;142:335-7. DOI: 10.1016/j.ajo.2006.03.003. [PMID:16876524]

Correspondence to:
Dr Stuart Keel
Vision and Blindness Prevention Programme
World Health Organization
[email protected]
Prof Mingguang He
Centre for Eye Research Australia; Ophthalmology
Department of Surgery
University of Melbourne
[email protected]
Dr Jingying Li
Department of Ophthalmology
Peking University Shenzhen Hospital
Shenzhen Peking University
The Hong Kong University of Science and Technology Medical Center
[email protected]