Chapter 126 – Degenerative Myopia
BRAD J. BAKER
• A poorly understood form of excessive axial myopia that can be associated with potentially blinding complications.
• Progressive global expansion with posterior staphyloma formation and secondary macular degeneration.
• Premature cataract formation.
• Vitreous syneresis, rhegmatogenous retinal detachment, and glaucoma.
Myopia is a common optical aberration. Physiological myopia, by far the most prevalent, is less than -6D in magnitude and is considered a normal biological variation. Eyes that have errors greater than -6D are said to have high myopia. The greater the myopia, the more likely are complications that can threaten vision. A subgroup of high myopes have axial lengths that fail to stabilize during young adulthood. The pathophysiology of this progressive, degenerative form of myopia is unknown.
EPIDEMIOLOGY AND PATHOGENESIS
Not all eyes that have myopia greater than -6D progress; nor does every eye that has progressive myopia develop degenerative complications. The worldwide distribution of those who have truly degenerative myopia is unknown, but the prevalence of progressive “pathological” myopia was surveyed by Fuchs more than 40 years ago. Among 15 countries in the study, progressive myopia was found in 0.3% (Egypt) to 9.6% (Spain) of their populations. Asians are known to have a high prevalence of myopia. That of progressive myopia in Japan was 8.4%. This wide variation implies that there is a genetic influence.
In the multiethnic United States, the prevalence was estimated at 2.1% in a U.S. Public Health Service study. Women are affected twice as commonly as men, and black Africans infrequently have progressive myopia. It is the seventh leading cause of blindness in the United States, and its effects generally occur at an earlier average age than those of diabetic retinopathy and age-related macular degeneration.
The pathogenesis of myopia in general, and progressive myopia in particular, is unclear, but both heredity and environment play a role. The mode of inheritance may be autosomal recessive or dominant, but it also can appear sporadically. Progressive myopia occurs commonly in association with
Ocular Manifestations of Degenerative Myopia
Deep anterior chamber
Angle iris processes
Lattice retinal degeneration
Scleral expansion and thinning
Decreased ocular rigidity
Increased axial length
Temporal crescent or halo atrophy
Macular lacquer cracks
Pigment epithelial thinning
Subnormal visual acuity
Visual field defects
Impaired dark adaptation
Abnormal color discrimination
Marfan’s, Ehlers–Danlos, and Stickler’s syndromes, and twin studies confirm its genetic basis.
The most widely accepted environmental influences are excessive near work and increasing formal education. Sustained accommodation and intraocular pressure (IOP), both basal and phasic, are suspected to influence axial elongation in eyes that have decreased scleral resistance,  but recent evidence questions both of these hypotheses. Topical atropine slows the progression of myopia in children, but this may be via a mechanism independent of accommodation. Further, it appears that at least some degree of active scleral growth and remodeling appears to be involved in pathological myopia. This may be regulated by various local growth factors, independent of central nervous system control. Experimentally, ocular growth can be governed by the application of plus or minus spectacles, and children who have threshold retinopathy of prematurity develop less myopia following peripheral retinal ablation. Understanding of these and other influences upon development of myopia is still too fragmentary to permit therapeutic application.
The more important anatomical and functional abnormalities found in extremely myopic individuals are listed in Box 126-1 .
Patients who have excessive myopia often have strabismus, especially exophoria and exotropia, and are more likely to develop premature nuclear sclerosis or, in some cases, posterior subcapsular lens opacities. Glaucoma is more common among highly myopic eyes and is particularly insidious. Its prevalence is related to the degree of myopia. Curtin found glaucoma in 3% of eyes that had axial lengths less than 26.5?mm, in 11% that had
Figure 126-1 A 28-year-old Caucasian woman experienced a central light flash followed by blurred vision in her -23.50D right eye. A, A subretinal hemorrhage is present in the fovea. B, A small wishbone-shaped lacquer crack was observed 13 months later. C, At 27 months from the original bleed, another such crack was noted along a temporal extension of the growing lacquer crack pattern. This was asymptomatic and the corrected acuity was 20/60 (6/18).
axial lengths in the range 26.5–33.5?mm, and in 28% of eyes that had axial lengths over 33.5?mm. Determination of glaucomatous changes are especially difficult in highly tilted optic discs, with posterior staphyloma adjacent to the myopic disc complicating the evaluation of visual field defects. Also, pigmentary and normal-tension glaucoma occurs more frequently in myopes.
Among the other serious complications of progressive myopia are vitreous syneresis and rhegmatogenous retinal detachment that results from peripheral tears. Such detachments usually are spontaneous, but they may occur after blunt ocular trauma or subsequent to cataract surgery, especially when complicated by capsular rupture and vitreous loss.
The abnormality seen in the myope that justifies use of the term degenerative is posterior staphyloma (ectasia), with its devastating secondary effects in the posterior pole. The progressively myopic eye expands in all its posterior dimensions, and the formation of an equatorial staphyloma with scleral dehiscence is not uncommon, especially in the superotemporal quadrant. Visual loss is most often due to macular involvement of a posterior pole staphyloma.  The deformity occurs in various locations, described by Curtin as posterior polar (disc and macula central), macula centered with the disc at the margin, peripapillary, inverse (in which the depression extends nasally from the optic nerve head), and an inferior type that involves the lower portion of the disc and the fundus below it. Complex patterns are termed compound staphylomata. Usually, the edge of the defect is sharper closer to the disc and more blended away from it. Staphylomata that are clear edged and deep in a young person may occasionally lose some definition as the scleral envelope enlarges with age.
As the scleral shell expands, the neural retina, pigment epithelium, and choroid stretch and thin to accommodate the area they cover. Tissue attenuation causes the fundus to have a pale, tessellated appearance. The pigment epithelial cells are flattened, and a reduction occurs in the thickness of the choriocapillaris and in the larger vessel layers and pigment of the choroid. This is evident especially within the staphyloma itself, where the fundus pallor is exaggerated by the increased visibility of the underlying sclera.
With time and progression, traction and tension phenomena are observed. The first is a pale, temporal crescent at the disc as the pigment epithelium and choriocapillaris are retracted from the disc’s margin toward the deepest area of the staphyloma. Bruch’s membrane is noncellular and elastic but has a limited capacity to stretch. If its elastic limit is exceeded, the internal tension is relieved by formation of microdehiscences called lacquer cracks. Acute lacquer crack formation near the fovea occasionally is signaled by photopsias and metamorphopsia ( Fig. 126-1 ). Defects in the overlying pigment epithelium may appear punctate, but eventually a linear pattern develops that coincides with the breaks in Bruch’s membrane. Continued break formation results in a reticular pattern that usually is most obvious in the deepest recess of the staphyloma and portends a guarded prognosis for central vision.
The lacquer crack defects usually slowly increase in width and grow in number. Other isolated, round, or irregular pigment epithelial and choriocapillaris defects may develop along the margin or within the staphyloma. If a choroidal neovascular membrane invades a crack, an abrupt macular hemorrhage may be produced. Although usually self-limited, the hyperpigmented fibrovascular scar that evolves (Förster–Fuchs’ spot) causes a central or paracentral scotoma. An area of choroidal and pigment epithelial atrophy develops and surrounds the scar ( Fig. 126-2 ). This extends and coalesces with areas of atrophy that advance from other lacquer cracks, eventually to produce large geographical areas of destruction in which sclera can be seen through the transparent neural retina. The process is usually bilateral and insidious. As paracentral fixation areas diminish, even low-vision aids become useless and ambulatory sight is all that remains.
Macular hole formation in extreme myopes may occur, but the exact mechanism is unknown. Whether attenuation of the neural retina and its supportive pigment epithelium and choroid are responsible is speculative. Vitreous syneresis and posterior vitreous detachment are more common and occur at an earlier age among high myopes than among others ; usually they are not accompanied by vitreomacular traction or an epiretinal membrane and only rarely produce a posterior rhegmatogenous retinal detachment.
DIAGNOSIS AND ANCILLARY TESTING
Myopes are recognized easily by their poor distance visual acuity that is improved by negative-power lenses. Degenerative myopia is a diagnosis made when clinical findings and extreme axial length occur together, as cause and effect.
The need for ancillary diagnostic testing is dictated by the preliminary findings. If a posterior staphyloma is detected or questioned, A and B scan ultrasonography can confirm its presence. Fluorescein angiography and, in some cases, indocyanine green angiography may demonstrate more extensive lacquer crack formation than is detected by ophthalmoscopy and can be used to rule out choroidal neovascularization.
The clinician who has taken a careful history and performed a meticulous examination will have no difficulty in diagnosing
Figure 126-2 Sudden loss of vision. This male Caucasian myope (right eye, -8.00D; left eye, -9.00D) suddenly lost vision to 20/400 (6/120) in the right eye at 35 years of age. A, A choroidal neovascular membrane invades the fovea. B, Fluorescein angiography demonstrates the central membrane that had not been treated. C, The patient underwent a scleral reinforcement procedure on both eyes. Fifteen years later the area of central choriocapillary atrophy has enlarged, but corrected visual acuity is a surprising 20/80 (6/24).
progressive myopia. Its signature deformity is posterior staphyloma. Although patients who have retinitis pigmentosa are frequently myopic, show secondary cataract and vitreous liquefaction, can develop macular degeneration, and have peripheral visual field defects, these are easily distinguished by other findings in most cases. Peripapillary atrophic changes, punched-out defects in the pigment epithelium, and macular neovascular lesions are seen in ocular histoplasmosis syndrome. Myopes are unprotected from acquiring this infection, but its characteristics are not easily confused with those of degenerative myopia.
Myopia of different degrees and incidence may be associated with a wide variety of disorders. Many of these are hereditary and all forms of inheritance are represented.  A selected listing is presented in Box 126-2 . Environmental factors also determine expression, but because the complex development of the eye can be misdirected by a number of code sequence errors leads to an unavoidable conclusion—no single “myopia gene” exists.
Some systemic disorders are diagnosed easily, conditions such as albinism and trisomy 21; others are more subtle. Because the cardiovascular complications of Marfan’s syndrome and congenital rubella and the orthopedic disabilities associated with Ehlers–Danlos and Stickler’s syndromes may produce morbidity and even mortality, prompt referral to medical and surgical colleagues is indicated if the patient has not been referred already.
Typically, the extremely myopic eye is enlarged in all its posterior dimensions, but particularly in its axial length. Anteriorly, the cornea may be slightly thinner and flatter than normal, with a deeper anterior chamber, and the angle recess shows iris processes attached to the trabeculum. The lens has a tendency to show early nuclear sclerosis. Defects in the zonular membrane are common and may present a challenge during cataract surgery. The ciliary body may be smaller than normal, although considerable variability exists.
Generalized scleral thinning is associated with increased scleral elasticity, or decreased ocular rigidity. Especially when combined with zonular dehiscence, this results in rapid vitreous fluid egress and global collapse when the eye is opened to atmospheric pressure. Sudden hypotony can result in a serous or hemorrhagic choroidal detachment during intraocular surgery. Anatomically, the sclera is not only thin but also has an abnormal constitution. The classic electron microscopic findings of Garzino have been corroborated by others. The collagen fibers are of much smaller average diameter than in a normal eye.
Systemic Associations of Degenerative Myopia
de Lange’s syndrome
Fetal alcohol syndrome
Pierre Robin’s syndrome
Further, the fibrils show greater interfibrillar separation and the normally tightly opposed and interwoven architecture of the collagen bundles gives way to a more uniformly lamellar and eventually amorphous appearance. Choroidal neovascularization may be evident through Bruch’s membrane dehiscences. 
The ultimate goal is to prevent myopia progression and posterior staphyloma with its associated visual loss, but currently no proven method exists by which to accomplish this.
In children, topical atropine can effectively slow enlargement of the myopic eye and the effect is sustained even after the drug has been withdrawn.  However, the possibility of long-term light damage to eyes that have dilated pupils has been investigated insufficiently. If this method is chosen, a thorough informed consent is required, and sun shielding and filters are advised. The effectiveness of atropine in eyes genomically destined to become pathologically myopic is unknown. Other approaches presumed to act via modification of accommodation include the use of bifocals, undercorrection of myopia, and part-time spectacle wear. Clinical trials report contradictory results, but the regulation of young primate eye growth has proved possible by using plus and minus lenses to blur the retinal image.
Because highly myopic eyes have reduced scleral resistance plus a tendency to develop glaucoma, many investigators have postulated that scleral expansion is caused by raised IOP. Pärssinen found a significant correlation between raised IOP and myopic progression among boys, but not among girls, while Quinn et al. noted that ocular tension is higher in children who have myopia than in nonmyopes. Controlled trials of IOP reduction have been reported.    Timolol maleate was employed,
all the subjects were children, and the focus was not on progressive degenerative myopia. Goldschmidt’s pilot study of 10 children showed a tendency for the children who had a reduction in IOP to slow in their progression of myopia, but Jensen’s 2-year study of 94 children did not prove timolol to be effective.  The possibility remains that optical and pharmacological methods, alone or in concert, may be devised to retard axial elongation.
If advancing myopia in children continues beyond pubertal years, follow-up at least yearly is indicated. A stereoscopic, indirect ophthalmoscopic, and biomicroscopic search for staphyloma formation is important and, if suspected, staphyloma formation is investigated further using A and B scan ultrasonography. Some of these eyes eventually stabilize as highly myopic but with no posterior complications. The ongoing evaluation of any peripheral lattice degeneration lesions that may be evident, especially in the event of blunt trauma or an acute posterior vitreous separation, is critical.
If staphyloma formation is detected, further caution is warranted. Biannual examinations may reveal lacquer crack development that is not heralded by a photopsia or blurred central vision. Once lacquer crack formation or areas of choriocapillary and pigment epithelial atrophy are present in a young adult, it becomes likely that the central vision will be threatened in time by advancing atrophy, choroidal neovascularization, or both. The traditional option in the United States at this stage has been to continue observation, while ophthalmologists in some eastern European countries advocate the use of various tissue extract injections, vasodilators, and scleral reinforcement. Although the value of reinforcement surgery is unproved,  it may have application in selected and obviously endangered eyes in which the disease continues to advance.
One step short of surgery, or in addition to it, is to lower IOP. No controlled trial has been used to confirm efficacy or assured safety. Until such information is available, and in the absence of other contraindications, the use of a tension-reducing agent in “normal” eyes seems not unreasonable and has been recommended. Relative ocular hypotension in eyes prone to develop tears in Bruch’s membrane may help to prolong central vision.
Other conservative measures include avoidance of eye rubbing, trauma, Valsalva exertion, and regular use of anticoagulants such as aspirin (unless required for systemic disease). Because topical corticosteroids frequently provoke a rise in IOP in the highly myopic eye, these also should be used with caution and with frequent tension checks.
Myopia-related choroidal neovascularization is a major cause of visual loss, especially when located in a subfoveal location. Photodynamic therapy has shown a statistically significant reduction in visual loss when compared with a placebo group after 1 year for subfoveal choroidal neovascularization associated with pathological myopia. The lesion could be classic or occult on fluorescein angiography if either was at least 50% of the total area. The median visual acuity following treatment was 20/64+2 in the treatment group and 20/80–2 in the control group, with 77% of treated patients losing fewer than 8 letters compared with 44% of the placebo group at 12 months. The average patient received 3.4 treatments during the study. Extrafoveal choroidal neovascularization may also be treated with argon laser photocoagulation. Confluent argon laser burns of diameter 100–200?µm delivered over 0.2–0.4 seconds are most effective. Whether laser treated or allowed to involute spontaneously, the cicatricial lesion eventually becomes surrounded by a zone of atrophy that slowly enlarges with time. This atrophy typically is relentless and may progress to compromise the central vision.
Macular hole formation and the less frequently encountered detachment of the posterior retina are problems that confront those who care for patients who have degenerative myopia. Even for those patients who are attended by surgeons trained and practiced in modern vitreoretinal surgical skills, these complications result in a poorer prognosis and increased risk. Modern vitreoretinal surgical techniques can restore vision in select cases.
COURSE AND OUTCOME
Because the degenerative form of progressive myopia is among the leading causes of legal blindness is testimony that today’s treatment methods do not offer a cure. Affected individuals cannot share in the optimism of the more numerous patients with low myopia that the development of keratorefractive techniques will help them, because the fundamental nature of their disease, axial elongation and posterior staphyloma, is not altered by such techniques. Hopefully, laboratory and clinical evidence will provide practical methods by which to reduce the risk of progressive myopia. Meanwhile, the management of degenerative myopia is that of its complications and the prognosis for patients is guarded.
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