Acquired Macular Diseases
Lorne Yudcovitch, O.D., M.S., F.A.A.O.
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Table of Contents
IntroductionBasic Macular Anatomy
Categories of Acquired Macular Diseases
Epiretinal Membrane
Macular Hole
Macular Pseudohole
Macular Lamellar Hole
Cystoid Macular Edema
Clinically Significant Macular Edema
Central Serous Retinopathy
Myopic Macular Degeneration
Toxic Maculopathies
Histo Maculopathy
Toxo Maculopathy
Angioid Streaks
Choroidal Rupture
Side-Note on CNVMs
Choroidal Folds
Retinal Folds
Idiopathic Juxtafoveal Retinal Telangiectasia
Idiopathic Juxtafoveal Polypoidal Chorioretinopathy
Disclaimer
Author Contact
Introduction
The optometrist is often faced with clinical challenges concerning macular disorders, both in terms of proper diagnosis as well as recommendations and treatment for the patient. Fortunately, current techniques such as scanning laser ophthalmoscopy and photodynamic therapy have helped assist with solving these challenges. Yet aside from recent technological advances, much of the diagnosis of macular conditions still relies on a thorough case history and careful examination by the practitioner.
This course will only discuss the acquired macular diseases - those macular diseases that may arise typically later in a person's life, rather than congenital hereditary macular disorders. As such, this course will not be discussing the hereditary macular disorders, examples of which are noted in Table 1 below:
Table 1.| Some Hereditary Macular Disorders |
| Fundus Flavimaculatus/Stargardt's Dystrophy |
| Best's disease (Vitelliform Dystrophy) |
| Dominant Drusen (Doyne's Honeycomb Dystrophy) |
| Pattern Anomalies of Retinal Pigment Epithelium |
| Central Areolar Choroidal Dystrophy |
| Rod Monochromatism (Achromatopsia) |
| Progressive Cone Dystrophies |
| Ocular Albinism/Oculocutaneous Albinism |
| Certain Forms of Retinitis Pigmentosa (i.e. inverse) |
| Mucopolysaccharidosis (MPS) Syndromes |
The classic forms of age-related macular degeneration (i.e. exudative or "wet" macular degeneration and non-exudative or "dry" macular degeneration) will also not be discussed in this course, as these macular diseases are fairly well known by the optometrist and highlighted in numerous other papers in more detail.
Basic Macular Anatomy
The macula comprises approximately a 1.5 mm diameter area 15 degrees temporal, and very slightly inferior to, the optic nerve. The retinal layers consist of (from innermost layer to outermost layer):
1. Internal limiting membrane (ILM)
2. Nerve fiber layer (NFL)
3. Ganglion cell layer
4. Inner plexiform layer
5. Inner nuclear layer
6. Outer plexiform layer
7. Outer nuclear layer
8. External limiting membrane
9. Photorecptors
10. Retinal pigmented epithelium (RPE)
The layers interior to the rods and cones are angled more towards the foveola (center) of the macula, creating the foveal depression. The nerve fiber tissue in this area is called Henle's fiber layer. Bruch's membrane, a collagenous tissue, lies below the retinal pigment epithelium, bordering the choroid. Figure 1 below shows the general macula anatomy, while Figure 2 shows ocular coherence tomography (OCT) and histological cross-section of the macula.
Figure 1. Left - Normal macular anatomy. Right – normal macular fundus appearance.
(Source Left : http://www.gene.com/gene/products/education/vascular/amd.jsp)
Figure 2. Above - Normal macula cross section as seen with ocular coherence tomography (Source: http://www.nyee.edu/macular-holes.html). Below – histological cross-section of the macula and underlying choroid. (Source: http://www.bu.edu/ histology/p/07901loa.htm)
Categories of Acquired Macular Disease
As stated above, acquired macular diseases are typically due to 'later-life'-based changes or etiologies. These etiologies are usually:
• Degenerative
• Systemic disease
• Trauma/surgery
• Toxic
• Idiopathic
The rest of the course will examine various acquired macular diseases. The author has attempted to present these conditions from the "most common" to the "least common" condition seen in practice.
Epiretinal Membrane
Epiretinal Membranes (ERMs) are relatively common macular disorders that go by several other names (premacular gliosis, cellophane maculopathy, surface-wrinkling retinopathy, preretinal fibrosis, and macular pucker). They are caused by retinal glial cell proliferation, where the internal limiting membrane (ILM) develops wrinkling and breaks that ultimately allow glial cells access to surface (Figure 4). It is postulated that these breaks may be created when posterior vitreous detaches from macula. ERMs usually affect otherwise healthy people, and are bilateral in 5 percent of cases. Their clinical appearance is dependent on density of the membrane and distortion of retinal vasculature near the membrane.
Figure 4. OCT of epiretinal membrane.
(Source: http://www.nyee.edu/macular-holes.html)
Cellophane maculopathy is a specific type of ERM. It typically appears as a translucent membrane with irregular light reflex or sheen, that is best detected with 'red free' light (Figure 5). Fine surface striae may form as it thickens and contracts, with tortuous supero- and inferotemporal vessels. The posterior vitreous is usually detached from the macula. Most patients are asymptomatic, or have slight metamorphopsia. Visual acuities are usually normal or slightly reduced.
Figure 5. Cellophane maculopthy (specific type of epiretinal membrane). Source: http://www.uams.edu/jei/patients/retina_services/macularpucker.asp
Macular pucker is a more severe form of ERM, with retinal wrinkling centered around the fovea and more severe blood vessel distortion (Figure 6). Some vessels may actually be obscured by the wrinkled ILM. Metamorphopsia and reduced visual acuities (20/40 to 20/60) are common with macular pucker. A pseudohole or cystoid macular edema (CME) may form from partial posterior vitreal detachment (PVD) with persistent adhesions to the macula.
Figure 6. Macular pucker. Note the extensive retinal wrinkling pulling the vasculature.
Secondary ERMs may be caused by:
• Retinal Procedures
• retinal detachment surgery
• pan-retinal photocoagulation
• cryotherapy
• Retinal Vascular Disease
• Intraocular Inflammation
• Trauma
Treatment of ERMs usually involve vitrectomy and membrane peeling (Figure 7). This is a very delicate procedure that removes the membrane. Ironically, it may cause a worse epiretinal membrane to form as an outcome. Membrane peeling is indicated only if significantly reduced visual acuities (i.e. worse than at least 20/40, with significant visual complaints) from the ERM are present.
Figure 7. Simple schematic diagram of membrane peeling procedure.
(Source: http://www.eyemdlink.com/EyeProcedure.asp?EyeProcedureID=50)
Macular Hole
Formerly called senile macular hole, these result from a perifoveal focal vitreous cortex contraction that pulls the macular tissue free from the choroid, resulting in a well-delineated round macular defect (Figure 8). The fovea is particularly susceptible to hole formation, due to the fovea being thin, avascular, and with lack of structural support. Hole formation is typically spontaneous and abrupt. It usually is bilateral in only 10 percent of cases.
Figure 8. Above - Macular hole, fundus view. Below – OCT of macular hole.
(Source: http://www.nyee.edu/macular-holes.html)
Etiologies of macular hole include:
• Idiopathic (affects mainly postmenopausal women)
• Severe Myopia (associated with posterior staphylomas)
• Trauma (vitreous traction or commotio retinae)
• Solar Retinopathy (very small lamellar hole or cyst, 2 weeks post-UV exposure)
Macular hole formation usually occurs in four stages, discussed in Table 2:
Table 2. Stages of macular hole with descriptions.
STAGE |
Findings |
I (Impending Macular Hole) |
|
II (Early Macular Hole) |
|
III (Developed Macular Hole) |
|
IV (Vintage Macular Hole) |
|
I II III IV
Figure 9. Stages of macular hole, fundus view (above) with OCT views (below). (Sources: http://www.rvrc.com/ps_dc_macularhole.cfm, http://www.eyetec.net/group7/ M37S1.htm)
Progression from stage I to II usually takes between one week and several months. Usually there is a quick progression from stage II to III hole formation. Visual acuity may improve slightly if the retinal elevation subsides. Eccentric viewing may also improve acuity slightly.
The Watzke-Allen technique (Figure 10) may help in diagnosing and categorizing the macular hole. The method involves moving a vertical slit lamp parallelpiped beam moved over macula using a high plus lens. The patient states if the beam is unaffected, distorts in the middle, or breaks/splits in the middle. These responses usually identify no hole, a partial or impending hole, and a full thickness hole, respectively.
Figure 10. Patient perception of the vertical slit beam while using the Watzke-Allen technique, based on no hole, early macular hole changes, and full thickness hole.
Fluorescein angiogram of macular holes shows hyperfluorescence of fluorescein in hole (Figure 11) due to the loss of retinal pigment epithelium (known as an RPE "window defect").
Figure 11. Hyperfluorescence of the macular hole (arrow) during arterial phase of a fluorescein angiogram.
Treatment of macular holes involve ILM peeling and vitrectomy. The goals of this surgery are to stimulate glial cell proliferation and migration into the macular area, as well as relieve vitreo-retinal traction in the macular area and posterior pole. The surgical procedure can be enhanced by indocyanine green (ICG) staining (although some surgeons think permanent toxicity to the tissue may occur by using ICG). The peeling and vitrectomy is usually followed by a gas or oil tamponade, which ten requires the patient to be face-down for at least 1 week, to allow proper retinal adhesion (Figure 12).
Figure 12. Patient in face-down position post-gas/oil tamponade retinal surgery.
A recent review on macular hole surgery outcomes demonstrated that macular hole closure is expected in over 90 percent of macular holes after one operation, and that closure approaches 100 percent with stage II or early stage III holes. Twenty-five to fifty percent of closed macular holes fail to achieve better than 20/50 acuities, however, and there is about a 20 percent risk of cataracts and retinal tears post-operatively. Despite this, surgery usually has beneficial effect on the patients' quality of life. Currently there are no large randomized clinical trials to establish the risks and benefits of macular hole surgery (1).
Macular Pseudohole
Macular pseudoholes, as the name implies, have the appearance of macular holes, but are cause vascular tortuosity around the macula. Unlike macular holes, visual acuity is usually good. There may be possible metamorphopsia. The macular tissue still has full thickness, unlike macular holes. Pseudoholes require close monitoring of retina. An ocular coherence tomograph may provide definitive diagnostic differentiation of a macular pseudohole.
Figure 13. Left - Macular pseudohole, fundus view. Right – OCT of pseudohole. Note the macular tissue still present (arrow) above the choroid. (Source: http://dro.hs.columbia.edu/pshole2.htm)
Macular Lamellar Hole
A macular lamellar hole essentially is a thin layer (lamella) of macular tissue that has lifted from the remaining macular tissue (Figure 14). A lamellar macular hole may be a precursor to a full macular hole. They may also be a 'self-healed' full-thickness macular hole. Lamellar macular holes may also result from macular hole surgery.
Figure 14. OCT of macular lamellar hole, which provides definitive diagnosis.
(Source: http://www.retinalphysician.com/article.aspx?article=100221)
Cystoid Macular Edema
Cystoid Macular Edema (CME) is an accumulation of fluid within the macula. The layers affected typically are the outer plexiform (Henle's fiber) layer and the inner nuclear layer (Figure 15).
Figure 15. CME. Top – histological cross-section. Bottom – OCT cross-section.
The breakdown of the inner blood-retinal barrier causes CME. Accumulation is centered around the foveola, with a loss of the foveal depression occurring. Macular thickening occurs with multiple cystic areas, resulting in a 'petaloid' (flower petal-shaped) pattern of edema.
CME is generally benign in short-term (hours-days), but long-standing cases (weeks-months) result in coalescence of the fluid-filled microcysts, which create large cystic spaces. These cystic spaces can create lamellar hole formation at the fovea, ultimately resulting in permanent visual acuity loss (Figure 16). Fluorescein angiogram shows the classic 'petaloid' leakage of dye (hyperfluorescence) in the arterio-venous phase that persists into late phase of the angiogram (Figure 17). Many diverse etiologies can cause CME. The causes are divided according to presence or absence of vascular leakage on fluorescein angiography (Table 3).
Table 3. Causes of CME based on presence or absence of vascular leakage.
CME WITH RETINAL VASCULAR LEAKAGE |
CME WITHOUT RETINAL VASCULAR LEAKAGE |
Diabetic retinopathy |
Certain types of retinitis pigmentosa |
Branch retinal vain occlusion |
Early stages of macular hole |
Pseudophakia or aphakia |
Nicotinic acid maculoipathy |
Idiopathic retinal telangiectasia |
With choroidal neovascularization |
Figure 16. OCT macula cross-section showing bullous cysts secondary to CME.
(Source: http://www.nyee.edu/fluid-accumulation.html)
Figure 17. Fluorescein angiogram showing classic 'petaloid' leakage pattern of CME.
(Source: http://dro.hs.columbia.edu/cme.htm)
Treatment of CME depends on underlying cause. Laser photocoagulation is used more often when CME is associated with some vascular cases (i.e. retinal vein or arterial occlusions). Systemic carbonic anhydrase inhibitors (i.e. Acetazolamide) are used post-cataract extraction in some cases, and in certain retinitis pigmentosa and intermediate uveitis cases. Steroids and non-steroidal anti-inflammatory drugs (NSAIDs) are sometimes applied topically, orally, by sub-Tenon's injection, or vitreal injection. Triamcinolone is currently a popular injectable steroid used to treat CME (2).
A recent study of 21 eyes that developed post-cataract extraction CME showed that intravitreal triamcinolone 4mg injection improved visual acuities two or more lines in 43 percent of patients and by one or more lines in 86 percent of patients. One-third of eyes injected with triamcinolone developed intraocular pressures (IOPs) of 22mmHg or more (all reduced with topical anti-glaucoma agents), and no other complications were noted (3).
Clinically Significant Macular Edema
Clinically Significant Macular Edema (CSME) is usually associated with diabetes mellitus (DM). It is the most common cause of visual acuity loss with DM (Figure 18).
Figure 18. CSME. Left – fundus view. Right – fluorescein angiogram of same eye
(Source: http://dro.hs.columbia.edu/dme.htm)
CSME is defined by using one or more of the following criteria:
– Retinal edema within 500 μm of fovea
– Hard exudates within 500 μm of fovea with adjacent retinal thickening
– Retinal edema 1DD (1500 μm) or larger, any part of which is within 1DD of fovea
CSME can occur alone or with other diabetic retinopathy findings. Ocular coherence tomography (OCT) has utility in identification of diabetic macular thickening (Figure 19). Fluorescein angiography typically identifies the leakage points causing the edema, assisting with localizing treatment.
Figure 19. OCT image analysis. Left – macular thickening from CSME (note the red central zone of the thickness map). Right – normal macular thickness.
(Source: http://wwwscielo.isciii.es/scielo.php?script=sci_arttext&pid=S0365-66912004 000600008&lng=es&nrm=iso)
Treatment of CSME may involve destructive laser burn applications to center of exudate rings. Ideally these ring centers should be 500 to 3000 μm from the fovea, to avoid applying the laser to the foveal area and damaging the fovea. If CSME persists, 300 to 500 μm zone treatment may be necessary if indicated. Grid laser treatment (typically applied in a spiral, concentric pattern) may be needed for diffuse retinal thickening more than 500 μm from fovea and temporal rim of optic disc. Pan-retinal treatment for neovasculoarization may actually induce macular edema, likely due to retinal inflammation from the treatment (Figure 20).
Figure 20. Laser treatments for diabetic retinal changes. White spots represent laser burns. Left – focal treatment. Middle – grid treatment. Right – pan-retinal treatment.
(Source: http://www.rochestereyecenter.com/diabetic_retinopathy.asp)
Far Right – fundus image of focal laser burns (scattered arcuate white spots – arrow).
Like CME, CSME treatment may also include intra-vitreal steroid injection (usually triamcinolone). A recent study (on patients with bilateral CSME) evaluated 4mg triamcinolone intravitreal injection on one, with the other eye a control. OCT central macular thickness scans at 1, 3 and 6 months was then performed. Central macular thickness was significantly lowered in injected eyes versus the control eyes, except at 6 months after injection, because of recurrence of macular edema in 9 of 17 injected eyes at that time. The study conclusion was that intravitreal triamcinolone effectively reduces macular thickening in the short term and improves visual acuities in most cases. Long-term effect still remains to be elucidated (4).
Central Serous Retinopathy
Central serous retinopathy (CSR), also called central serous chorioretinopathy, is typically a sporadic, unilateral, and self-limiting sensory retinal detachment at macula. Young to middle-aged young males are predominantly affected, with type 'A' personality and stress sometimes associated. It results from a focal break or gap in the RPE, with leakage of sub-retinal fluid through this gap (Figure 21). Fluorescein angiography typically shows a 'smokestack' and 'umbrella' or 'mushroom' hyperfluorescence within the macular detachment occurring during late venous phase (Figure 22).
Figure 21. OCT of CSR. Note the elevated retina and small RPE focal detachment.
(Source: http://www.rvscny.com/OCT%20Examples.htm)
Figure 22. CSR. Left – fundus appearance. Right – fluorescein angiogram showing classic 'mushroom' hyperfuorescence leakage.
(Source: http://retinalinks.tripod.com/photogallery.html)
Fairly sudden visual acuity reduction in one eye may be noted, with 20/40 or better visual acuities typically. A hyperopic refractive shift can occur, due to the shorter axial length to the macular plane. As a result of this hyperopic shift, visual acuity improvement to 20/20 with low plus may be possible. Other symptoms may include s relative scotoma, metamorphopsia, micropsia (smaller image sizes), and impaired dark adaptation. Occasionally the condition can be extrafoveal, and this author has seen a few patients with atypical symptomatic extrafoveal CSR that was revealed via fluorescein angiogram.
CSR usually presents as a shallow, round or oval elevation. The sub-retinal fluid may be clear or turbid, and the detached retina is transparent. Retinal vessels within the CSR area will cast shadows onto the attached RPE and choroid. The distinct smooth border gives a 'glistening' reflex. Sometimes retinal precipitates and RPE detachment may occur. Very rarely a bullous ('bubble') retinal detachment may occur, that shows shifting sub-retinal fluid and exudate.
Fortunately, approximately 80 percent of CSR cases spontaneously resolve, returning to normal or near-normal visual acuity in six months. The remaining 20 percent typically resolve in 1 year. Some mild metamorphopsia can remain, however. Some patients may retain permanent visual acuity reduction or disturbance, usually from a prolonged detachment or recurrent attacks (Figure 23).
Figure 23. Chronic CSR with pigment epithelial changes.
(Source: http://www.cgeye.org/main.asp?url=http://www.cgeye.org/dim.asp?navID=3)
Focal laser photocoagulation has been used to obliterate the leakage site of RPE in CSR, and may speed up resolution by a few months. This treatment does not typically improve the visual outcome, however. Argon laser application of two to three low-power intensity burns at 200μm spot size, 0.2 sec duration at leakage point are typically done. A new type of laser for treating patients with CSR, called a selective retina therapy (SRT) laser, is currently being investigated. Its use is for CSR in which associated pigment epithelial detachment has caused sub-retinal fluid formation. The laser selectively treats the RPE yet spares photoreceptors. This leads to outer blood-retina barrier reconstruction. After 1 month of SRT treatment, leakage activity was no longer noted in 80 percent of patients (5).
Myopic Macular Degeneration
Myopic macular degeneration is an infrequent but potentially serious finding that typically progresses during young adulthood. It is due to progressive enlargement of the globe, with associated chorioretinal degeneration. Sensory retinal and RPE detachments can also occur. The globe is typically concave, often from posterior staphyloma (elongation of the globe and associated chorioretinal tissue creating an 'outpouching'). Extensive choroidal and retinal thinning results, leading to atrophy of the RPE and choriocapillaris. The sclera may become visible over time due to this atrophy (Figure 24).
Figure 24. Myopic degeneration. Left – retinal thinning revealing choroid, with myopic disc. Middle – OCT showing concave globe from posterior staphyloma. (Source: http://www.eyetec.net/group5/M25S1.htm) Right – myopic chorioretinal thinning, exposing the sclera.
Lacquer cracks (breaks in Bruch's membrane) are an uncommon finding with extensive myopic degeneration, appearing in about 4 percent of highly myopic eyes (Figure 24). These appear as fine, irregular yellow lines that may branch and crisscross. Lacquer cracks may allow choroidal vessel growth through the breaks, leading to sub-retinal hemorrhages. Secondary pigmentary proliferation from this choroidal vessel growth over time is called a Foster-Fuch's spot. These usually appear as a pigmented lesion in the macular area (Figure 25).
Figure 24. Lacquer crack from myopic degeneration, in the macular area (arrow).
Figure 25. Foster-Fuch's spots (Left, middle, right) from myopic degeneration.
Toxic Maculopathies
Several medications and other exogenous substances can cause potential toxicity to the macula. Some of the main substances that can cause maculopathy include:
• Antimalarials
• Phenothiazines
• Tamoxifen
• Canthaxanthin
• Talc
• Solar/Phototoxicity
Antimalarial Maculopathy
Chloroquine (Nivaquine, Avlocor) and Hydroxychloroquine (Plaquenil) are used in treating malaria and rheumatological disorders (i.e. rheumatoid arthritis, lupus). Excess of 300g cumulative oral dose (250mg/day for 3 years) significantly increases risk of maculopathy. Hydroxychloroquine has less maculopathy risk than chloroquine, and as such is typically the preferred medication to prescribe (Figure 26).
Figure 26. Left – Plaquenil (hydroxychloroquine). Middle – Plaquenil "bullseye" maculopathy. Right – fluorescein angiogram of Plaquenil "bullseye" maculopathy.
(Source: http://www.kellogg.umich.edu/theeyeshaveit/side-effects/chloroquine.html)
The levels of maculopathy from antimalarials are directly related to duration and dose, and described in Table 4 below:
Table 4. Levels of maculopathy from antimalarials.
Level of Maculopathy Findings
Premaculopathy Scotoma to red target between 4-9 degrees
Established 20/30 to 20/40 BCVA, faint halo of RPE pallor
Bull's Eye
20/60 to 20/80 BCVA, dark ring surrounds halo
Severe
20/120 to 20/200 BCVA, pseudohole and atrophy
End-Stage
Legally blind, large RPE atrophy, pigment clumps
BCVA = Best-Corrected Visual Acuity
Antimalarials tend to concentrate in melanin-containing structures such as the RPE and choroid. Corneal deposits also can occur, but are relatively benign. The maculopathy, however, is potentially serious. A pre-treatment baseline retinal evaluation is recommended, and should include:
• Visual acuities
• Amsler grid
• Colour vision
• Visual fields (10-2, Macular Threshold)
• Dilated retinal examination
• Fundus photos
Post-treatment retinal evaluations utilizing the tests above should be performed minimum annually if no signs or symptoms are noted. Home Amsler grids should be provided for daily monitoring of the central vision in each eye.
Quinine is an antimalarial alkaloid compound that also reduces nocturnal muscle cramps. An overdose of quinine may cause cinchonism, an ocular complex which has the following findings (Figure 27):
– Visual acuity loss (can also occur with normal dose)
– Fixed and dilated pupils
– Retinal edema (unknown mechanism)
– Attenuated arterioles
– Constricted visual fields
– Optic atrophy
Figure 27. Optic atrophy and attenuated arterioles from quinine toxicity.
(Source: http://content.lib.utah.edu/cdm4/item_viewer.php?CISOROOT=/EHSL-WFH&CISOPTR=533)
Phenothiazine Maculopathy
Thioridazine (Melleril) and Chlorpromazine (Largactil) are each used in treating schizophrenia and related psychoses. Chlorpromazine is also used as sedative.
A normal dose of Thioridazine is 150 to 600mg/day, while Chlorpromazine is 75 to 300mg/day. Greater than 800mg/day of Thioridazine for a few weeks can cause retinotoxicity, while greater than 2400mg/day Chlorpromazine over many weeks can cause retinotoxicity. This retinopathy presents as pigment changes that create a 'salt and pepper' appearance to the macula (Figure 28).
Figure 28. Thioridazine (Melleril) "salt and pepper" maculopathy.
(Source: http://www.kellogg.umich.edu/theeyeshaveit/congenital/retinopathy.html)
Macular toxicity usually causes decreased visual acuities and poor dark adaptation. Coarse granular macular pigmentation usually appears first, which may not progress if cessation of the drug occurs. Later, geographic RPE/choriocapillaris atrophy with hyperpigmented clumps and plaques may occur with continued drug use.
Tamoxifen Maculopathy
Tamoxifen (Nolvadex, Emblon, Noltam, Tamofen) is an anti-estrogen used to treat breast carcinoma. It has few systemic side-effects at a traditional normal dose of 20 to 40mg/day. Current dosages prescribed today may be even less, reducing the prevalence of side-effects. Vortex keratopathy and optic neuritis can rarely occur, which usually is reversible on cessation of therapy.
Retinotoxicity presents as multiple superficial yellow crystalline ring-like deposits at the macula, that can cause visual acuity loss (Figure 29).
Figure 29. Tamoxifen maculopathy. Note the yellow crystalline deposits.
(Source: http://www.opt.indiana.edu/ce/syspharm/part2.htm)
Canthaxanthin Maculopathy
Canthaxanthin is an oral agent that enhances suntanning. Prolonged used over time can cause maculopathy. This appears as tiny glistening yellow dots arranged in a donut-shaped ring around both maculae. These deposits appear in the superficial retina (ganglion cell layer), and generally benign (Figure 30).
Figure 30. Canthaxanthin maculopathy. Note the ring-like crystalline deposits.
Talc Maculopathy
Talc is inert filler material for tablets, comprised of magnesium silicate. Historically talc was used as filler in the transport of rice grains. Talc has a more destructive association with substance abuse. Drug abusers typically crush tablets of cocaine, methylphenidate (Ritalin) or other narcotic in water, boil the suspension, and filter it before injecting it. Injection is typically by intravenous, subcutaneous, and/or intramuscular routes of administration. Talc particles enter the circulation and embolize in various tissues. Most parts of bloodstream including the retina will be infused with the talc deposits over a long period of time of injections.
Talc maculopathy appears as multiple tiny, yellow-white, glistening particles scattered throughout posterior poles of both eyes (Figure 31). The talc is more numerous in the capillary bed and small arterioles of perimacular area. Some patients can get macular edema, venous engorgement, punctate and flame hemorrhages, and arterial occlusion associated with the talc emboli. Talc retinal granulomas and neovascularization can also rarely occur. This author has noted cases of associated paramacular scarring on certain patients who have injected cocaine or Ritalin over several years and developed secondary talc retinopathy.
Figure 31. Talc maculopathy secondary to cocaine abuse.
The extent of talc corresponds with amount and duration of drug abuse. It is routinely found if the person has injected the equivalent of over 12,000 tablets. Most patients have no visual symptoms, and the visual acuities are usually normal. However, blur and /or blind spots in visual fields can occur. 'Microtalc retinopathy' is a variant of talc retinopathy, involving finer deposits. This type of retinopathy may be associated with nerve fiber layer (NFL) defects and 'glaucoma-like' visual field loss.
Talc maculopathy observation usually involves careful questioning of the patient's medicinal and social drug history. Ocular talc indicates excess lung involvement, whereby lung function may be compromised. Drug abuse counseling and possibly a pulmonary consultation may be needed. Annual retinal evaluations with fundus photography and threshold VF testing are recommended. If there are glaucoma risk factors along with visual field loss, ocular hypotensive medications may be indicated.
Solar Maculopathy
Solar maculopathy may be best diagnosed from specific patient history. Sun-gazing, eclipse viewing, or arc weld light exposure may cause this unique form of maculopathy, and detailed history questioning may be required to elicit a positive connection. Solar maculopathy usually develops two weeks after exposure. It appears as a very small, circumscribed lamellar hole or cyst on the foveola that may be dark in colour (Figure 32). Initially a small foveolar exudate or edema may be present. Phototoxicity, rather than thermal damage, is thought to cause it. The visual acuities may be normal, but a small central scotoma may be identified. When no causative etiology is found, solar maculopathy can be termed 'foveomacular retinitis'.
Figure 32. Solar maculopathy. Left – fundus presentation. Middle – close-up of fovea showing small circumscribed cyst. Right – OCT showing small foveal cyst.
(Sources: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-27492004000 200016, http://www.eyetec.net/group7/M37S1.htm)
Histoplasmosis Maculopathy
Histoplasma capsulatum is a fungal organism prevalent in the Ohio-Mississippi River Valley area. Inhalation of Histoplasma spores from chicken or bat feces can lead to Presumed Ocular Histoplasmosis Syndrome (POHS). The 'presumed' element of POHS refers to the fact that the organism itself has not been identified in tissue, but the histoplasma skin test is positive in 90 percent of the cases. POHS typically shows the classic triad of ocular findings (Figure 33):
1) 'Histo' spots – scattered, punched-out chorioretinal round lesions
2) Peripapillary atrophy
3) Choroidal nevoascular membrane (CNVM) - usually in the macular area
Figure 33. Presumed ocular histoplasmosis syndrome, showing 'histo' chorioretinal atrophy spots.
Choroidal neovascular membranes usually appear late in POHS. CNVMs usually are associated with a macular 'histo' spot, but can also occur from peripapillary atrophy. Fluid leakage through the CNVM can cause metamorphopsia, blurring of central vision and a central scotoma. The CNVM may appear as an elevated yellow-white or grey lesion that eventually leads to a macular scar. Sometimes spontaneous resolution occurs, while other times a sub-retinal 'ring' hemorrhage can occur around the membrane. Repeated hemorrhages can occur over a two-year duration. Finally, a fibrous disciform scar eventually forms (Figure 34).
Figure 34. POHS. Left – peripapillary atrophy and CNVM. Middle – fluorescein angiogram of sub-macular CNVM. Right - disciform macular scar from chronic CNVM.
Fluorescein angiograms and daily Amsler grid testing are needed to monitor the CNVM, and OCT may also be useful in monitoring the CNVM here. As a CNVM can occur in the other eye, close monitoring is essential.
Argon laser photocoagulation is the traditional method of treating CNVMs. Best results are usually if the CNVM is greater than 0.25DD from the fovea. Some success has been seen with proton beam irradiation to the fovea. However, this requires access to a cyclotron, and is both expensive and experimental. Photodynamic therapy (PDT) with verteporfin (Visudyne) for the treatment of subfoveal CNVM in POHS was recently evaluated in one study (Figure 35). Sixteen eyes with subfoveal classic CNVM associated with POHS were treated with PDT. The mean visual acuity improved from 20/45- to 20/30+ after and average of 21 months (range: 8-32 months) and an average of two PDT sessions (range: 1-6 sessions). Visual acuity was stable to improved in 81 percent of subjects. The study suggests that PDT could be helpful for patients with subfoveal classic CNVM related to POHS (6).
Figure 35. Visudyne (verteporfin), by CIBA Vision/Novartis.
'Toxo' Maculopathy
Toxoplasma gondii, a protozoan typically transmitted by cats, and Toxocara canis, a roundworm typically transmitted by dogs, can cause unique forms of retinopathy.
Toxoplasmosis can enter the ocular tissues and cause active chorioretinopathy. This may appear as 'headlights in a fog' during fundus evaluation, due to the active, white lesion being surrounded by a vitreal inflammation. Eventually, the inflammation subsides to leave a quiet, usually oval or round pigmented chorioretinal atrophic scar of variable size (Figure 36). Toxoplasmosis scars of the macula can cause severe (20/200 to 20/400 or worse) visual acuity reduction.
Figure 36. Toxoplasmosis. Left – active 'headlight in the fog' toxoplasmosis lesion, with adjacent old inactive lesions. Right – old inactive toxoplasmosis macular scarring.
(Sources: http://eyetowncenter.com/eyetc/windows/images.htm?id=203, http://www.ted montgomery.com/the_eye/eyephotos/ToxoplasmosisChorioretinitis.html)
Toxocariasis can invade the eye to form a focal inflammation in the macular area, ultimately quieting to form a central granuloma (Figure 37). Optic nerve and peripheral granulomas can also form. Contraction of granulomatous bands between the nerve and macula can result in a 'pulling' of the macula to the nerve, creating a changed fixation (heterotopia), usually making the patient appear exophoric or exotropic.
Figure 37. Toxocariasis maculopathy. Left – central toxocariasis granuloma. Right – fibrotic granuloma strand between the optic nerve and macula.
(Source: http://www.revoptom.com/handbook/oct02_sec5_4.htm)
Testing for 'Toxo' maculopathy includes performing an ELISA (Enzyme-Linked Immunosorbant Assay), which evaluates the patient's antibody-antigen complex, as well as performing indirect immunofluorescent antibody tests, which involves killed organisms exposed to the patient's serum with antihuman globulin labeled with fluorescein. Hemoagglutination tests (coating lysed organisms to the patient's red blood cells and exposing the red blood cells to the patient's serum to see if adherence occurs) may also be indicated.
Treatment of active toxoplasmosis involves pyrimethamine (Daraprim), sulfadiazine (with or without trimethoprim), clindamycin, and the newer drug atovaquone. Systemic steroids may be needed to quell the inflammation, and laser photocoagulation may be utilized to create a 'firewall' around lesion, possibly preventing it from spreading. Cryotherapy may be indicated for peripheral lesions, and vitrectomy may be needed in cases of recalcitrant vitritis and vitreo-retinal adhesions. Further damage may occur from these surgical options, however. Finally, annual monitoring of quiet scar lesions with photodocumentation is recommended.
Visual prognosis is not typically affected by use of multiple anti-parasitic medications, and there is lack of evidence regarding various therapies. No consensus has been made among uveitis specialists regarding specifics of treatment regimens. There is a need for prospective randomized studies on ocular toxoplasmosis management (7).
Angioid Streaks
Angioid streaks are crack-like dehiscences in the collagenous and elastic portions of Bruch's membrane. These streaks can lead to secondary RPE and choriocapillaris changes. Angioid streaks appear as linear grey or dark red linear lesions with irregular serrated edges, located more posterior to the retinal vessels. They may sometimes mimic retinal vessels in appearance. Eventually angioid streaks may link in a ring-like fashion around the optic nerve head (Figure 38). Tapered radiations from this ring develop over time. Fluorescein angiogram of angioid streaks show hyperfluorescence caused by RPE window defects over the streaks
Figure 38. Angioid streaks. Left – peripapillary streaks. Middle – fluorescein angiogram of same eye showing streak hyperfluoresence and leakage of choroidal vasculature above the fovea. Right – streaks mimicking retinal blood vessels in other eye. (Source: http://www.oculus.suite.dk/STRIAEANGIOIDES1.html)
OCULAR ASSOCIATIONS:
There are several ocular findings that may associate with angioid streaks.
'Peau d'orange'
('leopard skin spotting')
• Yellow speckled mottling, especially temporal to the macula
• May precede the appearance of angioid streaks
'Salmon spots'
• Peripapillary chorioretinal atrophy/scars
• Reticular pigment clumping may also associate
Optic nerve drusen
• May precede angioid streaks
• Associated with pseudoxanthoma elasticum diagnosis
Figure 39. 'Peau d'orange' ('leopard skin spotting') associated with angioid streaks.
(Source: http://www.pxe.org/virtpat/docs/peau.html)
Complications of angioid streaks include choroidal neovascularization which can lead to serous/hemorrhagic detachment of the fovea. Laser photocoagulation treatment of this is controversial. Choroidal rupture can also occur due to the fragility of the streaks, so avoiding contact sports is recommended. An angioid streak in the fovea can cause severe visual acuity loss.
SYSTEMIC ASSOCIATIONS:
Pseudoxanthoma Elasticum (PXE)
Pseudoxanthoma Elasticum (PXE) is a connective tissue disorder in which the dermis elastin, arterial walls and Bruch's membrane of the retina are affected (Figure 40). Abnormal mineralization and phosphorus in the collagen fibrils are the histological abnormalities in this condition. There are four types of PXE (two dominant and two recessive inherited forms). Eighty-five percent of PXE develop angioid streaks, usually in the second decade of life.
Figure 40. Systemic signs of pseudoxanthoma elasticum. Left. - dermis and elastin abnormalities in the digits Right – 'chicken skin' neck papules.
(Source: http://meded.ucsd.edu/isp/1994/im-quiz/pseudox.htm
'Gronblad-Strandberg Syndrome' is a combination of PXE and angioid streaks. Findings with this syndrome include:
• Skin lesions – 'chicken skin' neck papules
• Cardiovascular disease – atherosclerosis
• Hemorrhages – Gastrourinary, Gastrointestinal (usually in the first decade)
Hemorrhages associated with PXE can be fatal if not controlled.
Paget's Disease (Osteogenesis imperfecti)
Paget's disease is a chronic, progressive bone deformity that has a mild inheritance pattern (Figure 41). It may present with skull enlargement, long bone deformities and fragility, and kyphoscoliosis (deformed spinal column). Deafness is common, and angioid streaks occur in 2 percent of cases.
Figure 41. Kyphoscoliosis from Paget's disease.
(Source: http://www.gfmer.ch/genetic_diseases_v2/gendis_detail_list.php?cat3=698)
Ehlers-Danlos Syndrome
Ehlers-Danlos syndrome is a rare, dominantly-inherited collagen disorder caused by a deficiency of hydroxylysine. This results in thin, hyperelastic skin and tissue that heals poorly (Figure 42). Hyperextensible joints, leading to dislocations and arthrosis, can also occur. Cardiovascular disease that can lead to aneurysms and bleeds is not uncommon. Gastrointestinal and respiratory diverticula and diaphragm hernias may also present. Along with angioid streaks, several other ocular associations with Ehlers-Danlos syndrome include:
• Epicanthal folds
• Keratoconus
• High myopia
• Retinal detachment
• Blue sclera
• Lens subluxation
Figure 42. Ehler's-Danlos syndrome. Left – hyperelstic skin (above) and hyperextensible joints (below). Right – associated blue sclera and epicanthal fold.
(Source: http://www.pathologyoutlines.com/eye.html)
Hemoglobinopathies
Angioid streaks may also be associated with types of hemoglobinopathies, including several forms of sickle-cell and thalassemia.
Choroidal Rupture
Caused by trauma (usually blunt trauma), choroidal rupture typically appears as a yellow-white crescent-shaped subretinal streak, which occasionally fills with pigmentation over time (Figure 43). The rupture line is usually concentric to the optic disc, and may be single or multiple in number. Choroidal ruptures are generally not seen until days or weeks after trauma.
Figure 43. Choroidal rupture. Left – rupture in the macular area. Right – rupture inferior to the optic nerve head in concentric pattern.
(Source: http://www.tedmontgomery.com/the_eye/eyephotos/ChoroidalRupture.html)
CNVMs may develop within the rupture. Fluorescein angiograms are indicated in management of these, with laser treatment indicated within 72 hours after if a CNVM is seen that is greater than 200 μm from fovea. Home Amsler grid monitoring and evaluation for any new CNVMs is recommended.
A Side Note on Choroidal Neovascular Membranes (CNVMs)…
Many 'occult' macular causes of reduced vision can be due to choroidal neovascular membranes below the macula. We have seen that he more common etiologies of CNVMs include exudative (wet) ARMD, myopic macular degeneration, ocular histoplasmosis, angioid streaks, and choroidal rupture. Less common etiologies include iatrogenic (i.e. post-laser photocoagulation), tumours, optic nerve head drusen, and idiopathic causes.
The optometrist should utilize objective and subjective tests of central vision (i.e. ophthalmoscopy, Amsler grid, 10-2 threshold visual fields) as well as potential specialized testing (i.e. macular OCT, fluorescein angiogram) to determine if a sub-macular membrane is present. A relatively new instrument by Carl-Zeiss Meditec, called the PREVIEW Preferential Hyperacuity Perimeter (PHP) uses a specific stimulus (a small deviation or 'bend' in a vertical or horizontal line stimulus) to test a patient's central vision in detail, similar to a visual field test (Figure 44). After the patient responds to the stimuli, the instrument calculates if any small central defects or scotomas are present. The sensitivity of this test can be high enough to identify CNVMs before they are seen on a fluorescein angiogram, in some cases.
Figure 44. Left - simple schematic of choroidal neovascular membrane. Right – PREVIEW Preferential Hyperacuity Perimeter (Carl Zeiss Meditec).
(Sources: http://www.stlukesretina.com/html/retina_conditions.html)
Choroidal Folds
Choroidal folds are lines, grooves, or striae in the posterior pole, usually parallel horizontal, although they can be vertical, oblique, or irregular in orientation (Figure 45). The folds are most frequently around macular area. Elevated areas of the fold appear light yellow-white in colour, while the depressed areas of the fold (the valley or trough) appears dark. Receptor distortion in the folds can cause initial visual acuity reduction, with permanent RPE/retinal/visual acuity changes occurring if it becomes chronic.
Figure 45. Choroidal folds. Left – large area of folds over the posterior pole. Middle – smaller area of folds over the macula. Right – fluorescein angiogram of the folds.
Causes of choroidal fold can be idiopathic; however they are more frequent in hyperopes, as well as orbital disease such as retrobulbar mass, thyroid ophthalmopathy, or choroidal tumour (Figure 46). These conditions may mechanically displace the choroid, creating the folds. Posterior scleritis and ocular hypotony can also cause folds if they are severe and prolonged in presentation.
Figure 46. T1 and T2-weighted MRIs of a retrobulbar orbital mass pushing on the posterior globe of the right eye.
Choroidal folds should not to be confused with choroidal detachments. Choroidal detachments are usually due to a rapid IOP drop that persists (iatrogenic causes such as trabeculectomies/retinal detachment surgeries can sometimes cause this). Choroidal detachments involve a transudation of choroidal fluid into the suprachoroidal space (the space between sclera and uvea). "Kissing choroidals" (whereby the choroids detach on either side of the globe to touch in the middle of the vitreous) may occur (Figure 46). Most small choroidal detachments resolve spontaneously in 2 weeks. Cycloplegia with frequent steroid dosing may be needed to help elevate the IOP in the interim, along with prompt referral to a retinal specialist.
Figure 46. B-Scan ultrasound of choroidal detachments, forming the 'kissing choroidal' pattern. (Source: http://www.thehighlights.com/Merchant2/merchant.mvc?Screen=CTGY &Store_Code=H&Category_Code=Sep-16th-2005)
Retinal Folds
Like choroidal folds, retinal folds may involve any part of the posterior pole. Retinal folds are most commonly associated with Stage 3 retinopathy of prematurity (ROP), a condition of retinal hypoxia induced post-oxygen incubation after birth. The table below summarizes the 5 main stages of ROP.
STAGE RETINAL FINDING
1 Vitreal base haze, mild retinal pigmentation
2 Vitreo-retinal fibrosis, disc/posterior pole 'dragging'
3 More peripheral fibrosis, retinal fold
4 Partial ring retinal detachment
5 Complete ring retinal detachment
Idiopathic Juxtafoveal Retinal Telangiectasia
Idiopathic juxtafoveal retinal telangiectasia (IJRT) is the mildest form of a family of rare, idiopathic retinal vascular anomalies. IJRT involves the central macular area (Figure 47). The other vascular anomalies in the family are Leber's miliary aneurysms (moderate, mid-peripheral vascular changes) and Coat's disease (most severe vascular and exudative changes, usually in the more peripheral retina).
Figure 47. Idiopathic juxtafoveal retinal telangiectasia. Left – note oval hemorrhage with mild exudate temporal to the fovea. Right – fluorescein angiogram highlights letangiectic vessels endings temporal to and around the fovea.
(Source: http://dro.hs.columbia.edu/juxtafovtel.htm)
Retinal vessel dilation and tortuosity is typical of IJRT. Aneurysms and lipid exudate leakage is also common. IJRT primarily affects the retinal capillaries, and must be distinguished from secondary telangiectasias (i.e. due to diabetic or hypertensive retinopathy)
Idiopathic juxtafoveal retinal telangiectasia is usually in adults and either unilateral or bilateral. Visual acuity loss and macular edema and exudate may occur. The temporal or entire macula may be involved Sometimes IJRT may be mistaken for diabetic retinopathy or 'wet' ARMD. . Fluorescein angiogram is indicated, which may reveal microvascular anomalies and capillary non-perfusion near the fovea. Argon laser photocoagulation may sometimes be used for treatment depending on proximity to the fovea.
Idiopathic Juxtafoveal Polypoidal Chorioretinopathy
Also called polypoidal choroidal vasculopathy, idiopathic juxtafoveal polypoidal chorioretinopathy (IJPC) appears as peculiar red-orange spherical CNVMs in the macular area. Fluorescein angiograms show IJPC as unique branching CNVMs with round ends to the vascular fronds (Figure 48). As the name implies, the cause of this condition is unknown. Laser treatment may be warranted in some cases.
Figure 48. Idiopathic juxtafoveal polypoidal chorioretinopathy. Left – unique spherical CNVMs as seen on fluorescein angiogram. Right – OCT of IJPC (above) with fundus orientation/fluorescein angiogram (below)
(Source: http://www.revophth.com/2000/November/RPretinsider0011.htm)
Summary
To conclude, the optometrist must be aware of the variety of acquired macular conditions that may present, as well as the proper management of these conditions. Along with a thorough ocular and systemic case history, appropriate objective and subjective tests are needed in order to best help the patient. With the advent of relatively newer technologies to diagnose and treat macular disorders, the optometrist can have greater confidence in managing these conditions.
References
1. Smiddy WE. Macular Hole Update: 2006
http://www.retinalphysician.com/article.aspx?article=100221
2. Rafael Ernane AA, Cristina M, Michel EF. Intravitreal triamcinolone acetonide injection in the treatment of Vogt-Koyanagi-Harada syndrome Arq. Bras. Oftalmol. vol.67 no.3 São Paulo 5/6 2004
3. Konstantopoulos A, Williams CP, Luff AJ. Outcome of intravitreal triamcinolone acetonide in postoperative cystoid macular oedema. Eye. 2006 Sep 29
4. Audren F, et al. Intravitreal triamcinolone acetonide for diffuse diabetic macular oedema: 6-month results of a prospective controlled trial. Acta Ophthalmol Scand. 2006 Oct;84(5):624-30.
5. Klatt C, et al. Selective Retina Therapy in central serous chorioretinopathy with detachment of the pigmentary epithelium. Ophthalmologe. 2006 Aug 26
6. Postelmans L, et al. Photodynamic therapy for subfoveal classic choroidal neovascularization related to punctate inner choroidopathy (PIC) or presumed ocular histoplasmosis-like syndrome (POHS-like). Ocul Immunol Inflamm. 2005 Sep-Oct;13(5):361-6
7. Koo L, Young LH. Management of ocular toxoplasmosis. Int Ophthalmol Clin. 2006 Spring; 46(2):183-93
8. Idiopathic juxtafoveal polypoidal chorioretinopathy. http://www.revophth.com/2000/November/RPretinsider0011.htm
9. Kanski JJ. Clinical Ophthalmology – A Systemic Approach (4th Ed.). 1999. Butterworth-Heineman.
10. Alexander LJ. Primary Care of the Posterior Segment (2nd Ed.). 1994. Appleton & Lange.
11. Spalton DJ, Hitchings RA, Hunter PA. Atlas of Clinical Ophthalmology (3rd Ed.) 2005. Moseby-Yearbook Ltd.
12. Bartlett JD, Jaanus SD. Clinical Ocular Pharmacology (4th Ed.) 2001. Butterworth-Heineman.
13. Rhee DJ, Pyfer MF. The Wills Eye Manual (4th Ed.) 2002. Lippincott Williams & Wilkins.
14. Fraunfelder FT, Fraunfelder FW. Drug-Induced Ocular Side-Effects (5th Ed.) 2001. Butterworth-Heinemann.
15. Tasman, Yaeger. Duane's Clinical Ophthalmology on CD-ROM. 1999 Ed. Lippincott Williams & Wilkins.
16. Parrish II RK. Atlas of Ophthalmology. University of Miami Bascom Palmer Eye Institute. Current Medicine, Inc.
Disclaimer
The author has no proprietary or financial interest in any of the products mentioned in this article. Course materials are not for use outside of this continuing education purpose without prior author consent. Opinions by this author do not necessarily reflect the opinions of Pacific University or the College of Optometry.
Contact this author:
Dr. Lorne Yudcovitch
College of Optometry
Pacific University
2043 College Way
Forest Grove, Oregon
U.S.A. 97116
E-mail: yudcovil@pacificu.edu
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