Aniseikonia

Etiology

Optical Aniseikonia

Optical aniseikonia is caused by a difference in refractive error. A disparity in spherical refractive error between the eyes is called anisometropia, whereas anisoastigmatism describes dissimilarity in the amount or orientation of cylindrical error. Anisometropia causes a difference in image size, whereas anisoastigmatism causes a difference in image shape.

When the vertical astigmatic meridian has comparatively less plus dioptric power, or more minus dioptric power, objects appear vertically compressed or horizontally elongated in the affected eye. Conversely, objects appear vertically stretched and horizontally compressed when the horizontal meridian has less plus dioptric power. In addition to differences in the dioptric power of spectacle lenses, other parameters, such as the index of refraction, lens thickness, vertex distance, and base curve, affect spectacle magnification and can result in optical aniseikonia.

Changes in the cornea and crystalline lens can cause anisometropia and anisoastigmatism, whereas changes in the length of the eyeball, or axial length, or a difference in the refractive index of the vitreous cavity contents can only cause anisometropia and do not result in anisoastigmatism. Spectacle lenses may also cause a change in the shape of objects. High minus lenses can cause a barrel-type distortion, in which the corners of the image appear squeezed inward, and high plus lenses can cause a pincushion-type distortion, in which the corners of the image appear stretched outward. Unequal barrel or pincushion distortion between the 2 eyes can also result in optical aniseikonia.

Causes of Optical Aniseikonia

Caused by the cornea:

• Keratoconus is caused by thinning of a portion of the cornea and often affects 1 eye more than the other. Keratoconus causes asymmetrical progressive myopia and high amounts of astigmatism.[7] This condition can be inherited and is associated with eye rubbing, allergies, atopic disease, and some collagen vascular diseases.[8]
• Corneal edema can be caused by contact lens overwear; certain medications, such as amantadine for Parkinson disease, netarsudil for glaucoma, and belantamab mafodotin for multiple myeloma; corneal endothelial diseases, such as Fuchs dystrophy; and complications from cataract surgical procedures. 
• Many types of corneal stromal and surface diseases are categorized according to whether they are caused by injury, inflammation, infection, or dystrophy. 
• Corneal surgical procedures that may leave the patient with anisometropia are intentional, such as monovision correction, or unintended, such as unequal laser-assisted in situ keratomileusis, photorefractive keratectomy, or radial keratotomy. Radial keratotomy often results in progressive, unequal hyperopic changes that may eventually lead to anisometropia. Other surgical procedures that can cause optical aniseikonia include corneal epithelial scraping, corneal crosslinking, radial keratotomy, phototherapeutic keratotomy, and INTACS.

Caused by the crystalline lens

• Cataracts generally increase the refractive index of the crystalline lens, resulting in increased myopia. If one eye has increased cataract progression, aniseikonia can be the result.
• Unilateral crystalline lens removal resulting in aphakia was historically 1 of the most common causes of clinically significant aniseikonia. Advances in cataract surgical procedures and intraocular lens implantation have made aphakia-related aniseikonia less common.[9] However, monovision cataract extraction results in intentional anisometropia and can cause aniseikonia. Results from 1 study reported a 6.7% reoperation rate for binocular visual complaints.[10]
• Hyperglycemia has been reported to cause refractive changes of all types, even though in clinical practice, high blood glucose levels are generally associated with increased myopia. An accommodative spasm can occur due to medications such as pilocarpine or excessive time spent focusing.
• Multiple other medications, in addition to pilocarpine, are associated with refractive changes. These medications include topiramate, acetazolamide, sulfamethoxazole and trimethoprim, indapamide, promethazine, spironolactone, isosorbide dinitrate, bromocriptine, tetracycline, corticosteroids, hydrochlorothiazide, penicillamine, quinine, metronidazole, isotretinoin, and aspirin. Although the mechanism of action is not always known, in some medications, such as topiramate, the refractive change is caused by anterior movement of the lens rather than by changes in accommodation or refractive index. Lens subluxation usually increases astigmatism as it progresses and, after complete dislocation, results in a large hyperopic shift. 
• Lens subluxation can be caused by simple ectopia lentis, ocular diseases such as pseudoexfoliation syndrome and aniridia, and systemic diseases such as Marfan syndrome, homocystinuria, and Ehlers-Danlos syndrome.
• Unilateral cataract surgical procedure: Although cataracts are usually bilateral, they may develop at different rates, and surgical interventions may be spaced over time. In most studies, the second eye receives a surgical procedure immediately after the first procedure in only 30% to 40% of patients.[11][12] Many patients with a high refractive error before the surgical procedure may be left with anisometropia until the surgical procedure is performed on the second eye. If these patients desire spectacle correction, optical aniseikonia may occur. Another procedure that affects the refractive power of the eye at the lens plane is the implantable collamer lens. Although the implantable collamer lens is often used to correct high myopia, spectacle correction could cause aniseikonia if the lens is placed in 1 eye or if an erroneous power calculation results in anisometropia.[13]

Caused by the vitreous space

• Silicone oil is used for retinal tamponade and may cause hyperopic or myopic shifts depending on posture and the eye's phakic, pseudophakic, or aphakic status.[14]
• Intravitreal gas, such as sulfur hexafluoride or perfluoropropane, is used for retinal tamponade and may cause a large myopic shift of up to 50 diopters.[15]

Caused by a difference in axial length

• Anisometropia and the resulting aniseikonia, when due to increased axial length, can be congenital and, if left untreated, lead to amblyopia. Congenital anisometropia is predominantly caused by genetic predisposition, but congenital glaucoma can also cause the condition.[16][17]
• Developmental anisometropia is primarily due to genetic predisposition. 
• Strabismus can also trigger the development of anisometropia.[18]
• Iatrogenically induced changes in axial length occur in scleral buckle procedures. Results from 1 study showed that an average increase of 0.99 mm in axial length was associated with a 2.75-diopter increase in myopia.[19][20] Aniseikonia is a common problem and occurs in a significant percentage of patients after scleral buckle procedures.[20]

Retinal Aniseikonia

Retinal aniseikonia is caused by macular dragging or distortion,[2] and can produce central-peripheral rivalry-type diplopia, also known as dragged-fovea diplopia syndrome. Aniseikonia-induced diplopia of this type presents when the brain fails to align central vision but successfully fuses peripheral vision.[21]

Causes of Retinal Aniseikonia

• Macula swelling causes a pincushion-type distortion and micropsia.[22][23][24] Common causes of swelling include macular edema, which can result from central serous retinopathy, diabetic macular edema, cystoid macular edema, wet age-related macular degeneration, retinal vein occlusion, and other conditions. Because macular edema alters the axial length, defined as the distance from the cornea to the retina, macular edema can cause anisometropia and, consequently, optical aniseikonia. For every 1000 µm of elevation, about 3 diopters of increased hyperopia is expected. 
• Macular shrinking causes barrel-shaped distortion and macropsia.[24] The most common cause of involution is macular staphyloma. As with edema, for every 1000 µm of increased axial length, an increase of 3 diopters of myopia is expected. 
• Macula distortion can be caused by retinal dragging, scarring, inflammation, and infection. Common causes include epiretinal membrane, macular hole, vitreomacular traction syndrome, proliferative retinopathy (including diabetic and other types), vitreoretinal inflammation and strands, retinal granuloma, retinopathy of prematurity, and others.[2][25]

Altered Brain Function

Altered brain function can cause symptoms of micropsia and macropsia in conditions such as Alice in Wonderland syndrome, Charles Bonnet syndrome, migraine, and hypnagogic and hypnopompic hallucinations.[26][27]  Although these conditions may present with aniseikonia-like concerns, they can be ruled out because they generally affect both eyes. In theory, conditions that alter the visual pathways behind the retina can also create aniseikonia. However, no patients with this presentation have been reported in the literature. Neural adaptation to the reversal of optical aniseikonia, even when longstanding, has been well studied.[28]

Epidemiology

Aniseikonia has not been measured in the general population. A hospital-based survey of aniseikonia in patients with binocular vision complaints found that 7.8% had measurable aniseikonia, and 4% had disruption of fusion and stereopsis. The same report surveyed orthoptists in the US and found that the majority evaluate aniseikonia, and that treatment was limited to fitting contact lenses and occluding or fogging 1 eye.[29] Aniseikonia has been studied in specific populations, such as patients who have undergone a scleral buckle procedure. Results from 1 report showed that 6% of patients experienced aniseikonia after a scleral buckle procedure, and only 1% had persistent aniseikonia that could not be treated.[20]

Aniseikonia is also more common after unilateral cataract surgical procedures. Second-eye cataract surgical procedures are performed in about 70% of cases, leaving 30% of patients at risk for aniseikonia.[30] Results from 1 study found that 40% of all patients with unilateral or bilateral pseudophakia had clinical findings of aniseikonia.[31] Researchers developed various formulas to estimate the risk of aniseikonia following cataract surgery.[32][33]

Anisometropia is among the most common conditions leading to aniseikonia and, by definition, occurs when the refractive error differs by more than 1 diopter between the eyes. Results from 1 study showed that the prevalence of anisometropia was 1.96% at 6 months, 1.27% at 5 years, and 5.77% among those aged 12 to 15 years.[34] Results from a scoping study found that anisometropia is associated with greater refractive error. As higher refractive errors increase, a corresponding increase in aniseikonia is expected.[35]

Anisoastigmatism is present when astigmatism exceeds 1 diopter. Although anisoastigmatism is less well studied, the condition also occurs when more than 1 diopter of difference is present in 1 meridian. Anisoastigmatism can occur when relatively low astigmatism is present in each eye, but 1 eye has with-the-rule astigmatism, and the other has against-the-rule astigmatism. Results from 1 study showed that the prevalence of anisoastigmatism was 7.7% in children aged 6 to 7 years and 5.6% in children aged 12 to 13 years.[36]

The Sydney Myopia Study reported that, among children aged 6 years, anisometropia and anisoastigmatism were more common in patients with myopia and were associated with amblyopia, exotropia, low birth weight, and older maternal age. Results from the same study revealed that anisometropia was associated with increased axial length and anisoastigmatism with higher corneal astigmatism.[37] Results from these studies did not reveal a racial or sex predilection. Researchers found that 31% of patients with congenital glaucoma also had anisometropia of 2 diopters or more.[38] Keratoconus was also strongly associated with anisometropia, with results from 1 study reporting a 5.5-fold increased risk of anisometropia of 1 diopter or more in patients with keratoconus.[39]

History and Physical

A thorough history that includes questions about asthenopia, headache, diplopia, dizziness, anxiety, imbalance, nausea, spectacle intolerance, distorted spatial perception, and previous ocular surgical procedures and ocular disease can alert the clinician to aniseikonia. Lensometry of the habitual spectacles, along with a full refractive evaluation that includes both objective and subjective data, can help determine the presence of anisometropia. Binocular testing, including tests of extraocular motility, ocular alignment, and stereopsis, can detect strabismus, ocular suppression, and amblyopia. Finally, a dilated fundus examination can rule out causes of optical aniseikonia, such as keratoconus and cataracts, and retinal aniseikonia, such as macular edema and epiretinal membrane.

Evaluation

Visual Acuity

Aniseikonia affects binocular vision relative to monocular visual acuity, with a maximum drop of 0.06 logMAR at 20% aniseikonia. A change of 0.06 logMAR is about half a Snellen line of letters and does not represent a large drop in visual acuity. Therefore, a comparison of monocular versus binocular VA should not be used to detect aniseikonia. Even at high levels of aniseikonia, visual acuity generally did not fall below the minimum required to drive.[40]

Testing for Retinal Aniseikonia  

• Amsler Grid: The Amsler Grid Test helps detect barrel and pincushion distortion, as well as evidence of dragging or other types of macular distortion. The test measures distortion in the central 20 degrees of the macula. Several types of Amsler Grid Tests are available. The most common version consists of a square grid of black lines on a white background with a black dot in the center. Variations on this grid include white lines on a black background, 1-degree versus 0.5-degree per square, and diagonal lines from the corners of the grid toward the center. Some grids have only horizontal lines or dots.[41]
• Other testing methods for metamorphopsia include an experimental 3D digital device and the M-Chart (Inami Co., Tokyo, Japan), which quantifies the degree of metamorphopsia, as well as the Preferential Hyperacuity Perimeter test, which assesses the central 14° of the macula.[42][43][44]
• Direct assessment of the retina through a dilated fundus examination is often supplemented by ancillary tests, such as macular optical coherence tomography. Macular optical coherence tomography is central to the diagnosis and correct treatment of underlying retinal pathology.

Testing for Optical Aniseikonia

In practice, the most common method for estimating aniseikonia is to calculate the difference in spectacle magnification between the 2 eyes. The formula for spectacle magnification for a thin lens is:

Spectacle Magnification = 1/(1 − dFsp),

where d is the distance in meters from the spectacle lens to the entrance pupil. The distance from the spectacle lens to the apex of the cornea, called the vertex distance, can be measured with a distometer. The vertex distance is generally close to 12 mm (0.012 m). The distance from the apex of the cornea to the entrance pupil is assumed to be an additional 3 mm (0.003 m). Therefore, d is usually close to 15 mm (0.015 m). Fsp is the power of the lens in diopters.

Application of this formula to a +1 diopter lens positioned at a vertex distance of 12 mm yields a magnification of 1.5%. In contrast, a −1 diopter lens positioned at the same distance produces 1.5% minification.[33] Clinicians often use a rule of thumb that 1 diopter of anisometropia produces about a 1% to 2% difference in image size.[45] Online calculators are available to clinicians to make these calculations quickly and easily. Corneal topography, or manual keratometry when corneal topography is unavailable, can be used to assess for corneal steepening or flattening as a cause of anisometropia.[46]

Optical and Retinal Aniseikonia Tests

A relatively simple test compares the size of diplopic images. In this test, the clinician induces diplopia with a horizontal or vertical dissociating prism. The image width or height can then be compared. Lenses of different sizes are then held in front of 1 eye until the perceived sizes of the 2 images are equal. A lens of a certain size provides a certain percentage of magnification. Size lenses are not commercially available but can be manufactured. Different magnification percentages for size lenses are achieved by creating a lens that acts as a small afocal telescope. The telescope magnifies in 1 orientation and minifies in the other.

Size comparison of images observed by each eye can also be made during the alternating cover test. Instead of creating diplopia with a prism, the clinician compares the perceived size during the alternating cover test. Size lenses are then used to magnify the smaller appearing image to match the size of the initially larger image.[5][47]

The Turville Test evaluates aniseikonia in the vertical meridian. Using a device developed by Morgan, in which the 2 eyes are dissociated, each eye sees 2 horizontal lines separated by a vertical line. An unequal distance between the horizontal lines on each side indicates aniseikonia. Size lenses can, again, be used to make the lines an equal distance apart in each eye.[48]

Testing for aniseikonia can be done with a Maddox Rod and 2 light sources. The Brecher Test employs a Maddox Rod placed over 1 eye to dissociate the 2 eyes. Dissociation can also be achieved by placing a Maddox Rod over each eye. This method is called the Miles Test. The 2 lights are separated horizontally or vertically to measure horizontal or vertical aniseikonia, respectively. Size lenses can then be used to eliminate a difference in the separation of the lights.[49]

The Robertson Technique employs a Maddox Rod placed over 1 eye and a light source that is moved away so that the observer's visual axis does not pass through the optical center of the spectacle lenses. When anisometropia causes optical aniseikonia, the Prentice rule predicts a greater displacement of the image passing through the higher-plus lens. This displacement can then be neutralized with a prism. The amount of prism required to neutralize the image displacement is then converted to an aniseikonia percentage. Because the observed image is offset from the optical center, this test assesses dynamic aniseikonia rather than the static aniseikonia that occurs when an observer evaluates a nonmoving image.[50][51]

The Awaya New Aniseikonia Test (Good-Lite Company, Tokyo, Japan) uses red-green glasses to dissociate the 2 eyes and a booklet with red and green semicircles of different relative sizes. The observer finds the image where the semicircles appear to be the same size. If, in reality, the semicircles are a different size, a diagnosis of aniseikonia is made. The degree of aniseikonia can also be determined from this test.[52]

An autostereoscopic smartphone was programmed to display half-moon images similar to those in the New Aniseikonia Test. The autostereoscopic effect allows the 2 eyes to be dissociated. In the test, the sizes of the 2 half-moon images are compared until they are deemed equal. The percentage difference in actual size between the 2 half-moon images represents the amount of aniseikonia present.[53]

The Aniseikonia Inspector Version 3 (Optical Diagnostics, Culemborg, The Netherlands) employs red-green glasses to dissociate the eyes and displays a red and green line on a computer screen. The lines can be oriented vertically, horizontally, and diagonally, and the program allows the observer to match the apparent length of the 2 lines. The lines are adjusted twice: at the start of the test, 1 line is displayed 25% smaller, and the second time, the same line is displayed 25% larger. The average of the 2 test results is used to determine the level of aniseikonia. One advantage of this test is its ability to assess a wide range of aniseikonia.[54]

The space eikonometer is a very accurate test and is considered the gold standard for measuring aniseikonia. The test requires single binocular vision with visual acuity of 20/60 or better and the ability to perform a relatively complex task: aligning 4 lines so that they are equidistant around a central target. The device was developed and sold by American Optical in 1951 and is no longer in production. The device can measure up to 5% of aniseikonia. Adelbert Ames developed the device in the 1940s, and the space eikonometer is therefore also called the Ames eikonometer.[5][55]

The Contrast-Balanced Aniseikonia Test is useful for patients with anisometropic aniseikonia who also have suppression and amblyopia. The intensity or brightness of the image presented to the amblyopic or suppressed eye can be increased to enable better comparison of the perceived sizes of the 2 images.[50] Emerging technologies, including tablets and cell phones, will improve test administration and accessibility.[56]

Treatment / Management

Treatment of Retinal Aniseikonia

Medical treatment: Medical treatment generally focuses on addressing the underlying chorioretinal disorder. The most common treatment for aniseikonia, contact lenses, does not treat retinal aniseikonia. Contact lenses can create similarly sized images on the macula, but if the retina is swollen (edema) or stretched (high axial myopia), the photoreceptors will be spread out over a larger area, and the image will appear smaller. Optical solutions that produce images of different sizes on the retina, such as iseikonic lenses or specially designed combinations of contact and spectacle lenses, are difficult to obtain, expensive, and technically demanding to create. Retinal aniseikonia generally presents with significant asymmetry, including prismatic, pincushion, barrel, and oblique forms, which cannot be treated optically, such as with iseikonic lenses or contact lenses. Most causes of retinal aniseikonia, such as central serous chorioretinopathy, macular edema, and epiretinal membrane, are unstable, making optical treatment impractical. Results from studies have shown that treatment for epiretinal membrane reduces aniseikonia to varying degrees of success.[57](A1)

Optical treatments 

Contact lens and spectacle lens combinations: A high-minus contact lens can be combined with a high-plus spectacle lens to create spectacle magnification that can offset retinal micropsia. This approach is also called a Galilean telescopic solution. The opposite combination, a high plus contact lens and a high minus spectacle lens, can offset retinal macropsia. Iseikonic spectacle lenses, when available, can be a good solution because the size of the image projected onto the retina can be adjusted to accommodate retinal swelling or stretching. 

Treatment of Optical Aniseikonia

Treatment of optical aniseikonia has many solutions.

Reduction of vertex distance: The shorter the vertex distance, the lower the spectacle magnification; although reduced vertex distance cannot eliminate aniseikonia, this simple step often reduces the condition to acceptable levels.

Contact lenses: Contact lenses are positioned very close to the entrance pupil of the eye, and even highly divergent lens powers will produce only minor aniseikonia. Therefore, using contact lenses in 1 or both eyes to fully correct the patient's refractive error is a highly effective way to reduce optical aniseikonia to tolerable levels.

Contact lens-spectacle and lens combinations:  Often, eliminating anisometropia with a contact lens that corrects only the difference between the anisometropic spectacle lenses is most desirable. Spectacle lenses often provide superior correction for presbyopia and astigmatism, are generally more effective at filtering different wavelengths of light, such as in sunglasses and blue-light–blocking lenses, and offer protection. In these cases, only 1 eye is fitted with a contact lens, reducing costs and the risk of contact lens–related infection and inflammation. A special pair of isometropic spectacles is then prescribed to be worn in combination with the contact lens.

Undercorrection of 1 spectacle lens: When neither surgical intervention, contact lenses, nor iseikonic spectacles is an option, anisometropia may be reduced by undercorrecting or overcorrecting 1 of the spectacle lenses. Although this approach may cause blurred vision in 1 eye, undercorrection or overcorrection may allow better depth perception.

Neuroadaptation: Evidence suggests that rapid neuroadaptation can occur in response to the onset and surgical reversal of aniseikonia.[13][28] Therefore, in some cases, when other solutions are unavailable, prescribing an anisometropic spectacle prescription may allow neuroadaptation and some degree of binocularity.(B3)

Refractive surgical procedures, including laser-assisted in situ keratomileusis, photorefractive keratectomy, and radial keratotomy, are common methods to correct optical aniseikonia.[58][59] Clear lens exchange, also called refractive lens exchange, is a procedure in which the crystalline lens is surgically removed and replaced with an intraocular lens implant. This procedure is used less often to treat aniseikonia, but with the advent of high-quality multifocal intraocular lenses, many surgeons and patients feel the benefits outweigh the relatively small risk of serious complications, such as infection and retinal detachment.[59] Phakic intraocular lens placement is a procedure in which a lens is implanted inside the eye without removing the natural crystalline lens. Although some studies have reported adequate safety and efficacy, the potential risks of corneal decompensation, retinal detachment, and elevated intraocular pressure also make this a less common treatment for aniseikonia.[60][61] Secondary intraocular lens placement is the placement of an intraocular lens in an aphakic eye or to replace a deficient lens. Advances in intraocular lens technology, specifically light-adjustable lenses, have enabled a highly precise isometropic refractive endpoint.[62](B2)

Iseikonic spectacle lenses work by altering the vertex distance, base curve, center thickness, and index of refraction of the spectacle lens material to provide magnification of 1 lens compared with the other. The formula for total magnification produced by iseikonic lenses is:

Total Magnification = Shape Factor Magnification × Power Factor Magnification,

Shape Factor Magnification = 1/[1 − (tD1/n)],

Power Factor Magnification = 1/(1 − hDv),

where t is lens thickness, D1 is the base curve, n is the index of refraction, h is the vertex distance in meters, and Dv is the dioptric power of the lens.

The impact of magnification by alteration of lens variables is summarized by the following principles:

• Increasing vertex distance (h): increases magnification for plus lenses and minification for minus lenses.
• Steepening the (front) base curve (D1): increases magnification and decreases minification for lenses of all powers.
• Increase lens thickness (t): increases magnification and decreases minification for lenses of all powers.
• Increase lens power (Dv): increases magnification for plus lenses and minification for minus lenses.
• Increase index of refraction (n): decreases magnification and increases minification.

In optical aniseikonia due to anisometropia, the lens power (Dv) is fixed; 4 other variables affect the design of iseikonic lenses: base curve, center thickness, index of refraction, and vertex distance.[63] If the difference between the eyes is up to 3 diopters, iseikonic lenses are usually an effective solution. At the maximum correction of 3 diopters, the iseikonic lens would look very different due to a large difference in center thickness and base curve. Occlusion of 1 eye is a last resort solution but may be used to avoid dangerous situations, such as driving with diplopia, or while waiting for other solutions to be implemented.

Advantages of Contact Lenses for Aniseikonia

• Contact lenses are the most effective and convenient way of eliminating optical aniseikonia.
• Contact lenses can be combined with a spectacle lens to create a magnifier to treat retinal aniseikonia.
• Contact lenses can usually be dispensed immediately from the trial lens inventory at the initial visit, and the lens power can be adjusted quickly in cases of changes in refractive error or aniseikonia, making them a convenient solution for unstable conditions and for patients requiring immediate intervention.

Disadvantages of Contact Lenses for Aniseikonia

• Many patients may not be able to wear contact lenses due to allergies, dry eye, or problems handling the lenses. 
• Contact lenses alone can not treat retinal aniseikonia.

Advantages of Iseikonic Lenses

• Iseikonic lenses can treat both optical and retinal aniseikonia.
• Iseikonic lenses may be the only option when surgical intervention or contact lenses are not possible.

Disadvantages of Iseikonic Lenses

• Finding a local source for these lenses can be difficult. The advent of optical vendors offering iseikonic lenses online that will assist with lens design provides hope that this solution will be used more often.
• One lens is usually heavier than the other, creating an uneven weight distribution.
• One lens is generally thicker than the other. This thickness difference is cosmetically unattractive and can make frame selection difficult.
• The iseikonic lens induces prism and distortion.
• One eye will appear larger than the other, affecting the patient's cosmesis.

Differential Diagnosis

Anisometropia causes induced prism. When anisometropia is accompanied by asthenopia, diplopia, nausea, imbalance, and headache, clinicians generally assume that aniseikonia is the cause. However, anisometropic spectacles can cause similar symptoms due to either optical aniseikonia, resulting from a difference in spectacle magnification between the eyes, or induced prism when the patient looks away from the optical center of the lenses, according to the Prentice rule. Contact lenses can further contribute to potential confusion because they address both induced prism and optical aniseikonia. Differentiating between aniseikonia and induced prism as the cause of symptoms involves testing for aniseikonia using the methods discussed in the treatment section or observing whether a spectacle correction that does not require looking away from the optical center, such as separate single-vision glasses, alleviates the symptoms.

Altered brain function can cause micropsia and macropsia, and other distortions, and can occur in conditions such as Alice in Wonderland syndrome, Charles Bonnet syndrome, migraine, and other types of hallucinations.[26][27] Although these conditions may present with aniseikonia-like concerns, clinicians can generally rule them out because they typically affect both eyes and are only temporary. Retinal pathology is often associated with symptoms that can be confused with retinal aniseikonia. Because retinal aniseikonia is generally treated medically rather than optically, aniseikonia testing is usually not performed, and optical solutions are not pursued. Therefore, in many cases, it remains unclear whether symptoms are caused by retinal pathology or aniseikonia.

Prognosis

Optical aniseikonia generally has an excellent prognosis because most refractive conditions can be treated with surgical procedures or contact lenses. If neither a surgical procedure nor contact lenses is an option, aniseikonic spectacles are available. Aniseikonia following surgically induced anisometropia after monovision laser-assisted in situ keratomileusis or cataract surgical procedure is well tolerated when the refractive difference is 1 diopter or less.[64] However, aniseikonia and loss of stereopsis increase fall risk in asymptomatic older adults.[65] 

Retinal aniseikonia has a good prognosis in most cases. In retinal edema, central serous chorioretinopathy is generally a self-limited condition that resolves without treatment. Other causes of edema are generally treated successfully with medication or surgical procedures. In cases of macular shrinkage due to a staphyloma, no medical treatment is available. Although macropsia can be treated with aniseikonic spectacles, the associated barrel distortion cannot be treated. Results from 1 study of patients treated for rhegmatogenous retinal detachment showed that postoperative aniseikonia significantly reduced visual function only when the condition caused diplopia.[66]

Amblyopia

If aniseikonia has resulted in amblyopia and the patient is younger than 9 years, treatment in accordance with the Pediatric Eye Disease Investigator Group guidelines may significantly improve visual outcomes. Results from studies showed that aggressive and early amblyopia therapy combined with contact lens–based aniseikonia control is effective even in severe cases of anisometropia, which may occur in Straatsma syndrome.[67] If aniseikonia has caused amblyopia and suppression of one eye, and the patient is older than 9 years, the prognosis is considerably worse.

Complications

Complications of aniseikonia include the following:

Amblyopia: When aniseikonia is missed in children during the amblyogenic period, which ends at 8 to 10 years of age, the condition can result in permanent vision loss.

Intractable visual symptoms:  When aniseikonia is undetected or inadequately treated, the effect on visual function can be substantial. Ongoing symptoms may include asthenopia, dizziness, diplopia, reduced ability to perform visual tasks, and headache. 

Loss of binocular function: When aniseikonia cannot be treated, the patient may develop suppression or strabismus. In the presence of persistent diplopia, the patient may choose to occlude the eye. Ocular occlusion results in a loss of binocularity and depth perception.

Loss of the benefit of ophthalmic surgical procedures: Ophthalmic surgical procedures, such as scleral buckle procedures, monocular cataract extraction, or corneal transplant procedures, generally result in an excellent monocular visual outcome. When aniseikonia interferes with binocular function, patients may feel functionally worse after the surgical procedure than before it. 

Contact lens complications: Treatment with contact lenses increases the risk of contact lens–related dry eye, corneal infection and inflammation, allergies, and increased stress related to contact lens insertion and removal technique and complications.

Iseikonic lens complications:  Iseikonic lenses can induce prism and distortion, and their use is often challenging. The lenses also affect the patient's cosmetic appearance due to the magnification of 1 eye. Inadequately fitted iseikonic lenses can result in unequal weight distribution, leading to spectacle discomfort.[68]