Myopia, commonly called short-sightedness, is characterised by the need for optical correction with lenses of negative power to achieve maximum distance visual acuity. Several ocular diseases such as retinal detachment, glaucoma and, in particular, choroidal neovascularisation (CNV), are more common in people with higher levels of myopic refractive error. Choroidal neovascularisation is the occurrence of newly formed vessels in the macula that often leads to a fibrotic pigmented scar causing a blind spot in the centre of the visual field.
Epidemiology
The prevalence of any level of myopia varies among different ethnic groups. Its prevalence in the US was about 25% in one study whereas a recent review reported values as high as 70% to 90% in Asian populations. In a multicentre study in the US myopia was four times more prevalent in children of Asian descent than in white children.
The degenerative form of myopia, called high or pathologic myopia (PM), is associated with potentially blinding conditions such as retinal detachment, macular degeneration and glaucoma. Pathologic myopia has been defined in recent reviews as a refractive error of at least -6 diopters or -8 diopters. Complications of pathologic myopia may occur at lower levels but they are more common when refractive error is -8 diopters or worse.
The prevalence of PM has been reported to be up to 2% in the US but it is much more common in Asian countries. In Eastern Europe 1% of the population is affected by myopia of at least -6 diopters and up to 8% of the Japanese population is affected. In a survey of 11,000 students aged 18 in Taiwan myopia of at least -6 diopters was found in 24% of girls and 18% of boys. The prevalence of a defect of -8 diopters or more is 0.2% to 0.4% in the US and 1% of the general population in Japan.
Pathologic myopia is associated with excessive and progressive elongation of the eyeball. This results in a variety of fundus changes such as hypopigmentation, tilted optic nerve and lacquer cracks (breaks in Bruch's membrane), with or without posterior staphyloma (deformity of the eyeball profile at the posterior pole). As elongation of the globe is a key feature of PM an axial length of 26 mm or 27 mm has been adopted as a biometric definition. A value of 26.5 mm or more has been adopted as an inclusion criterion in a recent therapeutic randomised controlled trial.
Pathologic myopia is an important cause of blindness and visual impairment, especially in the 50 to 75 years age range. Choroidal neovascularisation is the most common vision-threatening macular complication observed clinically in PM; for example, PM was found to be the cause of CNV in 60% of people under the age of 50 who were seen at a referral clinic.
As for age-related macular degeneration, CNV associated with PM may become bilateral. In a study of 325 highly myopic eyes of 218 patients, approximately 1 in 10 developed myopic CNV in 130 months average follow up. The incidence of CNV in the fellow eyes of patients with pre-existing myopic CNV was significantly higher than that in eyes of patients without pre-existing CNV (35% compared to 6%). Lacquer cracks at the macula were a risk factor for this event. Combining the overall 10% cumulative incidence estimate from this study with the prevalent number of people with myopia -8 diopters of more, an approximate 11-year cumulative incidence rate of 2 to 4 per 10,000 would be obtained.
Presentation and diagnosis
Early symptoms of CNV include blurred central vision and metamorphopsia (objects appear distorted). Although CNV due to PM is usually associated with less retinal destruction than in age-related macular degeneration the disease carries a substantial risk of severe visual loss. Visual acuity will become 6/60 (20/200) or worse in 40% to 75% of affected eyes within a few years from the first diagnosis of CNV. The visual prognosis is worse among patients aged 50 or more. People with bilateral CNV usually have a level of central visual loss that causes impairment of activities such as reading, driving, recognising faces and finding small objects. Orientation is usually mildly or not impaired except in the most severe cases. The disease may have a substantial economic impact on individuals and families because most people affected are of working age.
Choroidal neovascularisation in PM is usually readily diagnosed with fundus examination. The CNV is often seen as a subretinal elevation with a varying degree of hyperpigmentation that may be associated with subretinal fluid and haemorrhage. After several months the CNV often evolves to a macular fibrotic scar. In the long-term a large area of chorioretinal atrophy centred in the macula may occur around the central hyperpigmented CNV, a picture called Foster Fuchs' spot. Fluorescein angiography is necessary for diagnosis when CNV is suspected on the basis of symptoms and fundus examination. It usually shows a hyperfluorescent spot corresponding to the CNV that leaks dye during the exam. Fluorescein leakage is usually mild with respect to lesions seen in age-related macular degeneration and it is more evident in recent and active than in scarred lesions. Moreover, fluorescein angiography provides more accurate information about the location of the CNV with respect to the centre of the macula, called foveola and commonly identified as the centre of the foveal avascular zone (FAZ). The proximity of the CNV border to the centre of the FAZ is the main criterion used for anatomical classification of myopic CNV. Only lesions that are not subfoveal are usually considered for photocoagulation.
Treatment options
During the last three decades laser photocoagulation has been the only effective means of treating CNV associated with PM and age-related macular degeneration. Its effectiveness in the latter disease was demonstrated by the studies of the Macular Photocoagulation Study (MPS) Group. Its use in subfoveal lesions has been limited to a few select cases and only in patients with age-related macular degeneration because normal retinal tissue is also destroyed at the treatment site causing an absolute scotoma. Since myopic CNV has been reported to be subfoveal in 1/2 to 3/4 of eyes at presentation photocoagulation can rarely be applied.
Recently, photodynamic therapy has greatly expanded the possibility of safely treating myopic CNV. However, the randomised controlled trial that evaluated photodynamic therapy for myopic CNV had limited power to truly assess its effectiveness due to its limited sample size. Other treatment modalities, such as submacular surgery or macular translocation, have not gained popularity because their effectiveness has never been demonstrated in large randomised controlled studies and because of safety concerns.
Discussion
Given the insufficient data reporting and the small size of the two randomised controlled studies in this review the effectiveness of laser photocoagulation for treating myopic non-subfoveal CNV remains unestablished. However, only initial and final visual acuity were reported. Therefore, it was impossible to extract sufficient data for comparisons at fixed time intervals as per protocol. Furthermore, the small number of eyes assigned to the three wavelengths (nine per group) allowed for little power to detect even clinically meaningful differences in visual and anatomic outcomes. The follow up was also too short to allow for a sufficient part of the disease course to be observed. Follow up was always less than two years, the limit considered appropriate in this review.
Follow up at the first time-point varied markedly. Survival analysis can take account of loss to follow up, provided that patients enrolled during a certain period are carried on to the date representing the end of the study. Under such a design it is unlikely that other factors potentially associated with treatment are responsible for loss to follow up. However, such analysis was not available in this publication. Furthermore, in 1990 a differential loss of control participants was reported.
Observational studies are prone to several sources of bias, especially if retrospective. In Secretan 1997 there was an imbalance of baseline visual acuity, which was significantly worse in untreated eyes. The authors tried to reduce bias with stratified analyses by baseline visual acuity group. They found a significant difference in favour of photocoagulation at two years. No difference was found at five years, a pattern that is similar to that in one randomised study included in this review. While comparisons between groups can be biased in an observational study it may be useful to provide other types of data, such as on safety. In Secretan 1997, CNV recurrence was 72% at five years among treated eyes, with 64% of eyes having a dry scar at the last examination. The mean largest linear diameter of laser scar in disc diameters increased from 0.38 mm at baseline to 0.83 mm at one year, up to 1.56 mm at five years for those who needed only one laser. For eyes with recurrence, these values were 0.47 mm, 1.27 mm and 1.72 mm respectively. Although visual prognosis was not correlated to laser scar enlargement, this complication of photocoagulation could be a cause of delayed visual loss. The risk of inadvertent photocoagulation of the foveola with immediate visual loss is also unknown.
Conclusions
Implications for practice
Laser photocoagulation of CNV that does not involve the fovea has been shown to be effective in reducing the risk of further visual loss in age-related macular degeneration and in other types of CNV. However, its effectiveness for treatment of CNV associated with pathologic myopia is only presumptive, despite its widespread use during the last three decades. Observational studies suggest that the enlargement of the laser scar might lead to retinal pigment epithelial atrophy involving the foveal centre in the long-term, a picture similar to the natural course in some eyes affected by this disease. When ophthalmologists offer laser photocoagulation as a treatment option for myopic patients with non-subfoveal CNV they should state that it is able to anatomically stop the lesion growth in some cases, but that the balance between the possible resulting visual benefit and harm is unclear.
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