Features of choroidal neovascularization in elderly eyes with high myopia not meeting the definition of pathological myopia

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The current study compared CNV in the eyes of elderly people with HM not meeting the definition of PM with mCNV and nAMD to determine the clinical characteristics of high myopia CNV. Given the increased frequency of MM in patients over 40 years old and the age of onset of AMD, patients over 40 years old were included in this study.23.24. The results of the comparison with the mCNV group showed that more men were in the high myopia CNV group, patients had significantly shorter AL, significantly more occult and PCV, significantly greater GLD, significantly less LC , significantly more drusen of the other eye, and a significantly higher treatment frequency. Additionally, compared to the nAMD group, significantly younger patients had significantly fewer CNV types, significantly more LC, and significantly less drusen in affected eyes and other eyes. In other words, it can be inferred that high myopia CNV has a mixture of nAMD and mCNV features. CNVs that developed in the highly myopic eyes of patients under 40 years of age, which were excluded from the present study, may have different characteristics from those of elderly patients and require further investigation.

The development of MM is recognized as a major cause of visual impairment worldwide3,4,25. However, as a standard classification of MM has not been established, definitions differ between studies, making it difficult to perform a meta-analysis. In 2015, an international panel of myopia researchers, the META-PM Study Group, proposed a new classification of MM based on color fundus photography that defined PM as category 2 or better MM with the presence of a plus sign or posterior staphyloma, and defined mCNV, which is characterized as a plus lesion in the new classification, such as the presence of CNV in the PM eye3,4,8. mCNV is characterized by a classic small CNV lesion, usually with minimal exudative changes, and mostly accompanied by CL on indocyanine green angiography (ICGA) images.4,5,6. CNV is rarely accompanied by retinal pigment epithelial detachment or drusen. Similar to mCNV, nAMD causes CNV in the macula, which is also a cause of severe visual loss worldwide13. nAMD is often characterized by the presence of various types of CNV, ie, occult, classic, polypoid choroidal vasculopathy and retinal angiomatous proliferation; different sizes of CNV and drusen in the posterior pole14.15. nAMD has exudative changes that are vigorous and present in a variety of locations in the retina and subretinal and under the retinal pigment epithelium. The exact pathogenesis of mCNV and nAMD are unknown; however, they are thought to be distinct i.e. mCNV would result from mechanical damage to the retinal pigment epithelium, Bruch’s membrane and choroid due to ocular axial elongation as as myopia progresses26,27,28,29,30,31,32,33whereas nAMD is believed to result from a complex multifactorial interaction between metabolic, functional, genetic and environmental factors with age34.35. The response to anti-VEGF treatment also differs between mCNV and nAMD. mCNV requires fewer intravitreal injections to suppress CNV activity, while nAMD requires multiple intravitreal injections over a longer period of time4,5,6,9,10,11,12,16,17,18,19,20,21,22. The current results suggest that high myopia CNV does not match the features of mCNV or nAMD and is independent of both.

When cases of CNV with high myopia were compared between classic CNV and other CNV (occult CNV and PCV), significant differences in some clinical features were observed (Table 2). Compared to other CNV eyes, patients with classic CNV were significantly younger; and had significantly smaller GLD, significantly more CL, and had received significantly fewer treatments at 12 and 24 months. The classic CNV cases had mCNV-like features, while the other CNV cases had nAMD-like features. Since there was no difference in AL between the two groups, we hypothesized that CNVs of HM not meeting the definition of PM might be a mixture of mCNV and nAMD. In the present study, in the high myopia CNV group, the number of treatments was significantly higher in patients with occult CNV and PCV than in patients with classic CNV. Therefore, it may be appropriate to follow the nAMD treatment strategy when CNV or occult PCV is seen on angiography, even if the eye’s AL meets the definition of HM.

Another important aspect of the pathogenesis of high myopia CNV is the progression of MM. Hayashi et al. followed 806 highly myopic eyes for 5 to 32 years and reported the pattern of long-term MM progression25, that is, 40.6% had MM progression over a mean follow-up period of 12.7 years. Therefore, high myopia CNV in this report is defined as CNV occurring in the HM but less than grade 2 of the MM; however, some cases may progress to category 2 or higher MM during follow-up, and the diagnosis may be divided into mCNV or high myopia CNV depending on the time of diagnosis in some cases. Additionally, although the present study excluded patients younger than 40, these patients often have grade 1 or 0 MM and are not classified as having mCNV according to the criteria of the META-PM study group.3. However, some reports have suggested that fundus findings suggestive of PM may already be present in early childhood, so the diagnosis of mCNV in patients younger than 40 may require further investigation.36.

Corbelli et al. studied the incidence and characteristics of AMD in 874 of 442 patients with HM and reported that 11.9% had AMD, half of which were dry AMD and half were nAMD37. They also reported that 75% of n-AMD cases had CNV type 1 and that the mean number of intravitreal injections during the first year in treatment-naïve eyes was 3.8 ± 1.5. Our study was similar to this report in that there were more PCV and occult CNV (CNV type 1) cases than classic CNV (CNV type 2) cases in the high myopia CNV group, and more drusen were seen in PCV and occult CNV. case. However, the mean number of intravitreal injections during the first year in the high myopia CNV group was 4.5 ± 3.1 and in the high myopia CNV group 1.7 ± 1.1 for CNV conventional and 6.5 ± 2.2 for the other NVCs. The number of treatments for PCV and occult CNV was higher than those reported by Corbelli et. al. The reason for the discrepancy between our results and theirs may be that their inclusion criteria included an ocular AL greater than 25.5 mm or an equivalent sphere value less than -6 diopters (D), which differed of our inclusion criteria focused on MM progression. The number of treatments may have been affected by the difference in administrative methods, i.e. they used pro re nata and we used a modified Treatment and Extension (TAE) regimen.

The current study had several limitations, including its retrospective design and small sample size. The difference between anti-VEGF drugs and additional treatment regimens may have affected the results. Future prospective longitudinal studies with more patients over longer follow-up periods are needed to confirm the current findings. A small number of patients underwent photodynamic therapy or surgery during the study, which may have affected the number of intravitreal injections and visual outcomes.

In summary, we clarified the clinical characteristics and outcomes of CNV in elderly patients with HM who do not meet the definition of PM (high myopia CNV) by comparing them to mCNV and nAMD and showed that high myopia CNV may be a combination of mCNV and nAMD. . To our knowledge, this is the first report of elderly patients with CNV occurring in an HM that does not meet the definition of PM. Since the course and treatment outcome of high myopia CNV differs depending on the type of CNV, we should not just diagnose mCNV even in HM, but should perform angiography and develop a treatment strategy.

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