Etiology

Risk factors for retinal tear and detachment include myopia, a history of intraocular surgery, ocular trauma, lattice degeneration, a familial history of tear/detachment, and a history of either condition having occurred in the fellow eye. About half of all patients who have an RD are myopic. Historically, cataract surgery was known to increase the risk of RD. This risk has been mitigated to a significant extent by small incision surgery and other technical improvements. A history of posterior capsular rupture and vitreous loss increases the risk of subsequent detachment. YAG laser capsulotomy has also been identified as an independent risk factor.

The Patient

Clinical Symptoms

• Symptoms of an acute retinal tear include a sudden onset of floaters and debris, photopsia, and blurred vision. These same symptoms can occur in uncomplicated PVD. Photopsia associated with vitreoretinal traction is typically of very short duration, unlike the scintillations encountered with migraine or other vascular disturbances.
  
• When an RD has occurred, patients may additionally become aware of visual field loss, with the perception of a mobile shadow or curtain obscuring their vision. If the macula has become involved, there will usually be significant loss of central visual acuity as well. Patients with chronic, slowly progressive, or demarcated detachments, usually in the inferior retina, may be asymptomatic.

Figure 18-1. Retinal detachment. (Photo courtesy of Leonid Skorin Jr.)

Clinical Signs

Demographics

Approximately one of every 15,000 individuals has an RD in any given year. The incidence of retinal break is significantly greater, about 6%, but the majority of these breaks are small atrophic holes with a low potential for progression to RD. Historically, the peak incidence of RD has occurred between 50 and 70 years of age, with the frequency in that age group largely reflecting the incidence of both PVD and, to a lesser extent, cataract surgery. The current trend of fewer cataract surgery–related detachments may alter these numbers. Myopic detachments are most common between ages 25 and 45. There is another smaller peak in the teenage years, and these detachments are frequently of traumatic origin.

About 60% of RD patients are males, and trauma does not completely account for this propensity. Although familial patterns of RD are sometimes evident, most are sporadic. A large part of the familial risk profile is of an indirect nature, such as a genetic predisposition to myopia and/or lattice degeneration.

Horseshoe retinal tears occur with the greatest frequency in the superotemporal retina (~60%), followed by the superonasal quadrant. Traumatic retinal dialyses have a propensity to occur in the inferotemporal retina, particularly in the young. Retinal breaks occur at or anterior to the equator in about 85% of cases. Of all rhegmatogenous detachments, 50% have more than one break. The risk of RD in the second eye of an affected individual has been estimated to be about 10% to 15% in phakic individuals and 25% to 40% in aphakic or pseudophakic individuals.

Differential Diagnosis

The Treatment

Retinal Tear

Retinal Detachment

TABLE 18-1 Selected Results from the 2006 ASRS PAT Survey

Degenerative Retinoschisis

W. Craig Lannin

ICD-9: 361.10

     THE DISEASE

Although retinoschisis occurs in both hereditary (X-linked), juvenile and acquired, degenerative varieties, this discussion is limited to the much more common degenerative form. Degenerative (age-related, senile) retinoschisis is a relatively rare precursor to clinically significant (progressive) retinal detachment (RD), but can sometimes be difficult to distinguish from a chronic detachment. This differentiation is one of the most clinically important aspects of retinoschisis.

Pathophysiology

Degenerative retinoschisis represents a splitting of the retina, usually originating in the outer plexiform layer, and develops as a progression of peripheral cystoid degeneration.

Cystoid degeneration is found in the vast majority of adult eyes and begins with the development of tiny spaces within the outer plexiform layer. As the cysts enlarge, the spaces are bridged by glial cell fibers that extend from the external to the internal limiting membranes (ILMs). This process begins near the ora serrata and extends circumferentially and posteriorly but usually not posterior to the equator. Based on pathologic and, less distinctly, clinical features, cystoid degeneration may be subdivided into typical and reticular forms. The much less common reticular form has a greater potential to spread more posteriorly, beyond the equator.

With further enlargement of the cysts, the stretched glial pillars may eventually rupture, resulting in the development of retinoschisis. The inner wall of the schisis cavity typically consists of the ILM, the nerve fiber layer (NFL), the retinal vessels, and the inner plexiform layer. The outer wall is composed of degenerated elements of the inner nuclear, outer plexiform, and outer nuclear layers, with a relatively well-preserved photoreceptor layer. The cavity itself contains a viscous, hyaluronidase-sensitive mucopolysaccharide substance. The margins of the schisis are contiguous with areas of cystoid degeneration.

Some authors hold that the precipitating factor is an age-related degenerative change in the inner retinal layers related to vascular insufficiency and impaired cellular nutrition. This theory is supported by the increasing prevalence of retinoschisis with advancing age and by the association of vascular abnormalities seen with some cases of the condition. Other authors believe that vitreoretinal traction plays a role in the development and progression of retinoschisis. However, studies have failed to demonstrate that vitreoretinal relationships play a significant role in these events, and posterior vitreous detachment (PVD) in the presence of retinoschisis only rarely results in the development of a progressive, symptomatic RD.

The Patient

Clinical Symptoms

• The vast majority of patients (~99%) with retinoschisis are asymptomatic. Although retinoschisis causes an absolute visual field defect, most patients are unaware of these, except in those rare cases where the schisis extends posteriorly into the macular region. The reasons for the usual lack of recognition of the field cut include the typically very slow or lack of progression of the retinoschisis and the fact that nasal field loss associated with the usual temporally located schisis is often overlooked.
  
• Complications of retinoschisis include RD and vitreous hemorrhage. The localized, nonprogressive type of RD does not usually cause symptoms, but progressive, clinically significant detachments obviously do. Vitreous hemorrhage, causing an acute onset of floaters, or hemorrhage into the schisis cavity may rarely be associated with retinoschisis, but such hemorrhages are usually minor. Incidental PVD is a more common source of both vitreous hemorrhage and floaters in general.

Clinical Signs

Treatment is rarely required for degenerative retinoschisis. Only in those rare cases when progressive, clinically significant RD develops is surgery indicated. This usually entails cryotherapy and scleral buckle (SB) to close the outer wall breaks, most often with drainage of subretinal fluid. However, if the outer layer breaks are posterior, multiple, and/or large, cryotherapy with drainage and intraocular gas injection or vitrectomy techniques may be required. Patients with localized detachments, particularly those with demarcation lines, may be managed conservatively with periodic follow-up and education about the warning symptoms of progressive RD.

Prophylactic treatment of outer layer holes is of dubious value, as progressive RD rarely occurs and treatment is not without risk. This may be justified in cases where there has been a schisis-related detachment in the opposite eye.

Treatment of posterior extension of retinoschisis is rarely indicated, as the risk of macular involvement is quite small, and again treatment may be associated with complications.

All patients with retinoschisis should be followed-up at least every 6 to 12 months, depending on the duration and stability of the condition. They should be instructed to call promptly in the event of the development of symptoms suggestive of retinal tear or detachment.

Posterior Vitreous Detachment

Michael J. Trad

ICD-9: 379.21

     THE DISEASE

Pathophysiology

Posterior vitreous detachment (PVD) represents a cortical vitreous and hyaloid membrane detachment from the posterior retina. PVD occurs as a result of anterior contractional forces exerted by the overlying fibrous vitreous at the vitreous base, secondary to fibrillary degeneration and hyaloid membrane thinning. Fibrillary degeneration encompasses both syneresis (vitreal shrinkage) and liquefaction of vitreous. Gravitational forces also play a role in the inferior and anterior collapse of the vitreal body. However, PVD may also occur without collapse, although this is less common. PVD also is termed complete when it extends to the ora serrata or incomplete when involving only specific regional areas.

PVD is of greatest clinical concern as a result of its potential to cause retinal tears at preexisting sites of increased vitreoretinal adherence (lattice degeneration, retinal tuft, etc.). This tractional influence may result in retinal hemorrhage and tear; vitreous hemorrhage (those associated with PVD are usually small and self-limiting); vitreomacular traction syndrome; macular edema, hole, or epiretinal membrane (ERM); and retinal detachment (RD) (secondary to continuous flow of liquid vitreous through retinal breaks).

Etiology

PVD typically occurs as a normal consequence of aging but can also be associated or potentially linked with trauma, chorioretinitis, myopia, vigorous exercise or isolated head movement, heavy lifting, aphakia, and pseudophakia.

The Patient

Clinical Symptoms

• Floaters
  
• Transient photopsia
  
• Blurred vision
  
• Metamorphopsia

Clinical Signs

Prominent Signs

Demographics

• PVD rarely occurs in patients younger than 45 years of age unless associated with chorioretinitis or trauma.
  
• Vitreous detachment of the optic disc is present in approximately one-half of all patients older than 50 years of age.
  
• By age 65, approximately 31% of the population has experienced a complete PVD.
  
• Complete PVD is much more common than incomplete PVD.
  
• Up to 50% of PVDs are associated with photopsia.
  
• Approximately 90% of patients who report concurrent flashes and floaters have PVD, and 11% have retinal breaks.
  
• Retinal breaks occur in up to 15% of patients with symptomatic PVD.
  
• 7.5% of PVDs have an associated vitreous hemorrhage.
  
• Traction at the posterior pole resulting in macular edema occurs in about 2.5% of symptomatic PVDs.

Significant History

• Trauma
  
• Chorioretinitis
  
• May potentially be precipitated by aphakia, pseudophakia, myopia, heavy lifting, and vigorous exercise or isolated head movement

Ancillary Tests

Ocular assessment for PVD may include confrontation visual fields, Amsler grid, biomicroscopy, and dilated fundus evaluation.

The Treatment

No treatment for isolated PVD is necessary. Occasionally, Nd:YAG laser vitreolysis or pars plana vitrectomy (PPV) is employed for patients intolerant of floaters. Patients with no apparent retinal involvement at the time of initial presentation must be thoroughly educated as to the necessity to return immediately upon recognition of new floaters or flashes. It is this early stage in which symptomatology is detectable that is vital in providing a therapeutic window of opportunity for the prevention of RD. Differing opinions prevail as to both the usefulness and frequency of regular follow-up visits because retinal tears may occur anywhere from a few weeks to a decade after initial examination of uncomplicated PVD.

Idiopathic Epiretinal Membranes

Michael J. Trad

ICD-9: 362.56

     THE DISEASE

Pathophysiology

IERMs typically display little or no progression. However, some may grow and contract enough to cause irregular folding of the retina’s ILM and nerve fiber layer (NFL). In rare instances, significant vision loss can occur when further tractional forces result in cystoid macular edema (CME), macular holes, or retinal detachment (RD).

Etiology

ERMs have been described differently in the literature, depending upon their etiology, appearance, and/or clinical stage, and include idiopathic ERM, preretinal membrane, preretinal gliosis, preretinal macular fibrosis, cellophane maculopathy/retinopathy, crinkled cellophane, star folds, surface-wrinkling retinopathy, macular pucker, pigmented macular pucker, pigmented preretinal membrane, primary retinal folds, and silent central retinal vein (CRV) obstruction. Some ERMs may be associated with ocular and/or facial trauma, retinal vascular disorders (e.g., diabetes), vitreous hemorrhage, retinal breaks and detachment, intraocular inflammation (e.g., toxoplasmosis), photocoagulation, or previous anterior segment or vitreoretinal surgery. Most IERMs are idiopathic.

The Patient

Symptoms and signs of IERMs are dependent upon the extent of the disease process and the presence of secondary tractional sequelae, such as CME.

Clinical Symptoms

Typically, there are no subjective complaints, and IERMs are found on routine examination. However, patients may complain of blurred vision and/or metamorphopsia. Decreased depth perception, diplopia, and absolute scotoma are also infrequently observed.

Clinical Signs

• IERM is much more prevalent in patients over the age of 50 (6.4% of individuals within this age group are thought to have the condition).
  
• Unilateral IERM occurs in 70% to 90% of cases.
  
• Approximately 1% to 2% of unilateral cases eventually become bilateral.
  
• IERM affects both sexes equally.
  
• PVD occurs in 80% to 90% of cases.
  
• CME has been reported to occur in 16% of patients with IERM.
  
• In 77% of cases, vision is 20/60 or better, while 61% have acuity of 20/40 or better.

Significant History

• Usually none (possibly PVD)

Ancillary Tests

Ocular assessment of IERM would include best-corrected visual acuity, pupil assessment, Amsler grid, color vision, dilated fundus examination, and optical coherence tomography (OCT).

Fluorescein angiography (FA) is usually not necessary but may be indicated when acuity is worse than 20/40 (especially when a partial PVD is present), concurrent CME is suspected, or the condition occurs in younger individuals.

The Treatment

In most cases, surgical intervention is not warranted as IERMs are usually self-limiting with a final visual acuity of 20/40 or better. Patients are instructed on routine Amsler grid usage, and follow-up examinations are scheduled according to individual case severity.

Historically, surgery was considered only when visual acuity was 20/60 or worse and after contemplating preexisting permanent macular damage as well as anticipated surgical trauma. More recently, earlier membrane removal has been advocated for cases in which OCT demonstrates a disrupted photoreceptor integrity line. When surgery is performed, a pars plana approach with a closed intraocular microsurgical technique (vitrectomy with membrane peeling) is employed. Stabilization of visual acuity typically occurs 1 to 3 months postoperatively and in 83% of cases improves by at least two Snellen lines. ERMs recur at an incidence of approximately 3% to 4%.

Ocular Histoplasmosis Syndrome

Michael J. Trad

ICD-9: 115.02

     THE DISEASE

Pathophysiology

Ocular histoplasmosis syndrome (OHS) presents initially in the posterior pole, peripapillary area, and peripheral retina as a bilateral, multifocal choroiditis. Active “histo” lesions are comprised of lymphocytes, plasma cells, and macrophages and may disrupt Bruch’s membrane and subsequently damage the retinal pigment epithelium (RPE) and outer retinal layers.

It is believed that 10 to 30 years after the initial infection, in which inhaled particles of fungus enter the body, reactivation of the disease and subretinal neovascular membrane (SRNVM) progression may occur. A potential visually devastating maculopathy may ensue when SRNVM extension results in hemorrhagic RPE and/or neurosensory retinal detachment (RD), and ultimately disciform scar formation.

Etiology

Although cases of OHS may be found anywhere throughout the United States because of population migration, OHS typically affects individuals living in the so-called histo belt of the Ohio and middle Mississippi valleys, Alabama, Arkansas, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maryland, Mississippi, Missouri, Nebraska, Ohio, Oklahoma, Tennessee, Texas, West Virginia, and Virginia. OHS usually occurs in immunocompetent persons without overt systemic manifestations, but may present opportunistically in immunocompromised patients (e.g., AIDS).

The Patient

Clinical Symptoms

Patients are usually asymptomatic unless significant macular or peripapillary retinal involvement occurs. In these instances, blurred or distorted vision and field loss may be experienced.

Clinical Signs

Significant History

Past or present residence in the histo belt; past exposure to chickens, pigeons, or parakeets; immunodeficiency states (e.g., AIDS may reactivate OHS); stress may precipitate macular involvement.

Ancillary Tests

Ocular assessment for OHS may include visual acuity, color vision, Amsler grid, confrontation fields, pupils, biomicroscopy, tonometry, dilated funduscopy, fundus photography, and optical coherence tomography (OCT).

Laboratory studies are rarely necessary, as the diagnosis is usually made on fundus appearance alone. However, in rare instances, chest x-ray and HLA gene typing (DRw2 and B7 genes) may be utilized.

Fluorescein angiography (FA), indocyanine green (ICG) angiography, and OCT may be useful in cases of presumed or active maculopathy.

The Treatment

The Verteporfin in Ocular Histoplasmosis Study demonstrated efficacy for photodynamic therapy (PDT) of SRNVMs, and subsequently PDT has been utilized for subfoveal, juxtafoveal, extrafoveal, and peripapillary choroidal neovascular membranes (CNVMs). Anti-VEGF therapy has also been successful.

Recurrence of SRNVMs necessitates home Amsler grid testing, monitoring of systemic hypertension (HTN) (which may exacerbate recurrences), and yearly ocular examination (or more frequently if necessary).

Ocular Toxoplasmosis

Nicky R. Holdeman

ICD-9: 771.2—CONGENITAL TOXOPLASMOSIS

ICD-9: 130.0—ACQUIRED TOXOPLASMOSIS

     THE DISEASE

Pathophysiology

Toxoplasma gondii is the most common cause of infectious retinochoroiditis in the world, accounting for 30% to 50% of cases in otherwise healthy individuals. In addition to retinochoroiditis, the organism may also produce other functional changes including a dense vitritis, vitreous detachment, iridocyclitis, perivasculitis, retinal detachment (RD), neovascularization, cataracts, and glaucoma.

Recurrent retinochoroiditis occurs when tissue cysts release parasites that invade and destroy retinal cells. Since the organism is an intracellular parasite, the retina sustains the primary insult and the major damage. As they proliferate, parasites stimulate inflammatory reactions and the expression of vascular endothelial growth factor (VEGF), resulting in clinically apparent lesions. Factors related to reactivation of disease in otherwise healthy individuals are not known and recurrences cannot be predicted.

Etiology

T. gondii is a small obligate intracellular protozoan parasite affecting humans and animals; nearly one third of humanity has been exposed to this parasite. Multiplication occurs in the intestines of cats and the oocyst forms are shed in the stool. Cysts may remain viable in the soil for extended periods.

The most common routes of human transmission are by intrauterine infection, by ingestion of contaminated food or undercooked meat, or through inhalation of oocysts in cat litter.

The Patient

Clinical Symptoms

The patient will generally not complain of pain, but rather of an increase in floaters and a reduction of vision in the affected eye.

Clinical Signs

The appearance of a toxoplasmosis lesion varies depending on whether the infection is in an active or inactive state, and on the immune status of the patient.

Congenital infection has been estimated to affect 3,000 infants born in the United States each year. When primary infection of the mother occurs during pregnancy, there is a 40% chance of fetal infection. As a rule, IgG antibodies to Toxoplasmosis protect the fetus, but that is not always the case.

Recurrences often manifest between ages 11 and 40, with the mean age of first presentation being approximately 29 years. The disease is rather uncommon in early childhood and after the age of 50, but severe or acquired cases of ocular toxoplasmosis have been reported in older patients without suspected or documented immunodeficiency.

Recurrences have been observed in 49% of patients within 3 years.

Legal blindness (BCVA ≤ 20/200) in at least one eye may be expected in 24% of patients (i.e., macular involvement, vitreous hemorrhage, SRNVM, or RD).

Significant History

• Is the patient aware of having contracted any congenital infections?
  
• Does the patient eat raw or undercooked lamb, pork, or chicken?
  
• Is there an exposure to cats or cat litter?
  
• Infected water, organ transplantation, and blood transfusions are potential sources of transmission, but are rare in the Unites States
  
• Inquire about immunosuppression or risk factors for AIDS in patients with active bilateral, atypical, or multifocal lesions.

Ancillary Tests

The diagnosis of ocular toxoplasmosis is usually made by the classic fundus findings; however, several tests can be used to confirm clinical impressions or assist in atypical cases.

• Serology is supportive but not diagnostic in adults, as 20% to 70% of the general population will show positive titers.
  
• The most commonly used serologic tests are the IFA and ELISA for toxoplasmosis which can be done on blood, cerebrospinal fluid (CSF), and aqueous. These tests permit separation of IgM and IgG antibodies. The presence of IgM antitoxin titers indicates a recent acquisition of infection. Recurrent retinochoroiditis is usually associated with stable, low IgG titers and no IgM antibody. A positive test, even at a 1:1 dilution, corroborates the diagnosis.
  
• In difficult or atypical cases, anterior chamber paracentesis to detect local antibody production may be helpful. If IgG antibodies in the aqueous are higher than in the serum, the diagnosis is supported. In addition, polymerase chain reaction tests to detect T. gondii DNA in the aqueous can help confirm the diagnosis and help differentiate ocular toxoplasmosis from similar retinal lesions caused by herpes virus or other infectious agents.
  
• The Sabin-Feldman dye test, which was the original standard test for toxoplasmosis, requires working with live Toxoplasma organisms and is seldom used today.
  
• Fluorescein angiography and optical coherence tomography may be useful in helping to identify subretinal neovascular membranes and/or macular edema.

The Treatment

Large lesions, or those that (a) threaten the optic nerve, macula, or a large retinal vessel (b) cause excessive hemorrhage, or (c) induce a significant inflammatory response, are often treated with a combination of systemic steroids plus one to three antitoxoplasmic agents. It should be noted, however, that there is a lack of evidence to support routine antibiotic treatment for acute toxoplasmic retinochoroiditis and that treatment may be associated with adverse effects.

Corticosteroids are rarely employed in the treatment of immunocompromised patients and should never be used without antimicrobial therapy. Steroids are often given concurrently with antitoxoplasmic drugs to alleviate inflammation, especially when the lesions are located near the macula or the optic nerve.

• Prednisone 40 to 80 mg p.o. q.d. began after the second or third day of antitoxoplasmic therapy until day 10 and then tapered gradually over a period of 4 to 5 weeks. Stop steroids before discontinuing antitoxoplasma medications.

Antitoxoplasmic drugs include the following:

• Pyrimethamine—loading dose of 100 to 200 mg p.o. the first day and then 25 mg p.o. b.i.d. for 3 to 6 weeks. Follow complete blood counts and give folinic acid (leucovorin) 5 mg p.o. three to four times weekly to minimize bone marrow depression (thrombocytopenia, leukopenia, megablastic anemia). Continue leucovorin for 1 week after stopping pyrimethamine.
  
• Sulfadiazine—loading dose of 2 to 4 g p.o. the first day, then 1 g p.o. q.i.d. for 3 to 6 weeks depending on clinical response.
  
• Clindamycin—150 to 300 mg p.o. q.i.d. Useful adjunct to above therapy or may be used with only sulfadiazine. If the patient has a sulfa allergy, clindamycin may be used with pyrimethamine. Clindamycin concentrates in the choriod but is expensive. Monitor for pseudomembranous colitis. Limit treatment to 4 weeks.
  
• Azithromycin—500 mg on day 1 followed by 250 mg/d, alone or in combination with pyrimethamine, appears to be effective in treating sight-threatening lesions with fewer side effects than other antibiotics.
  
• Tetracycline—loading dose of 1 g p.o. on the first day, then 500 mg p.o. q.i.d. for 3 to 6 weeks.
  
• Trimethoprim (160 mg)/sulfamethoxazole (800 mg)—1 tablet p.o. b.i.d., with or without clindamycin. Many uveitis specialists concur that TMP/SMX is an effective therapy and is generally well tolerated. There is also some evidence that long-term treatment (every 3 days for up to 20 months) with TMP/SMX significantly reduces the rate of recurrence of retinochoroiditis in patients with a history of multiple previous recurrences.

Note: Since some of these drugs may have significant side effects, it is advisable to follow these patients with an internist.

Success has been reported with intravitreal injections of clindamycin and dexamethasone and may offer an additional treatment strategy in patients who are unable to afford or tolerate systemic therapy, or whose disease progresses despite systemic therapy.

Intravitreal injection of bevacizumab (Avastin) appears to be an effective and safe treatment in patients with choroidal neovascularization (CNV) secondary to ocular toxoplasmosis.

Anterior segment inflammation varies from a minimal response to a severe granulomatous iritis and is treated with topical cycloplegics (e.g., atropine 1% b.i.d.–t.i.d.) and/or topical steroids (e.g., prednisolone acetate 1% q.i.d.) as the need exists. Periocular corticosteroid injections can cause dissemination and should not be given.

Toxocariasis

Nicky R. Holdeman

ICD-9: 128.0

     THE DISEASE

Pathophysiology

Toxocariasis is a clinical syndrome resulting from parasitic invasion of human viscera with subsequent migration of the larvae to various organs. Most ocular damage results from the inflammatory response that occurs following death of the larva. Toxocara does not develop beyond the larval state in the incidental human host, and thus eggs are not found in the stool of humans.

Etiology

Toxocariasis most commonly results from infections with larvae of the canine roundworm, Toxocara canis. The adult worms live in the intestinal tracts of their primary hosts and release large numbers of eggs in the stool. The eggs can remain active and infective in the soil for months to years.

Human infections are generally acquired by young children who ingest the ova from soil or sand (geophagia) contaminated with animal feces, most often puppies. The embryonated eggs can also be acquired from contaminated raw vegetables or infected raw meat. The eggs hatch in the intestine and liberated larvae then penetrate the mucosal wall and are disseminated by the systemic circulation to the liver, lung, brain, kidney, striated muscle, central nervous system (CNS), heart, and the eye where they may produce an eosinophilic granulomatous inflammation. Remains of larvae are found within the granulomas, which contain eosinophils and histiocytes.

The Patient

Clinical Symptoms

Symptoms will vary depending on the organ involved. Children, usually before the age of 3, may develop acute systemic disease (i.e., visceral larvae migrans [VLM]). If so, the migrating larvae may produce symptoms such as malaise, fever, cough, skin rash, and/or abdominal pain.

Patients with ocular toxocariasis are usually older children or young adults, who complain of visual impairment in one eye, or may be referred for evaluation of leukocaria or strabismus. Eye pain is not typical in this condition.

Clinical Signs

Patients with visceral larva migrans may demonstrate lymphadenopathy, hepatomegaly, fever, wheezing, or a variety of other findings with diverse organ invasion.

In the eye, toxocariasis can have the following three different presentations:

Figure 18-8. Toxocara posterior pole granuloma with fibrous vitreous bands extending from the lesion.

Note: It is rare to have VLM and ocular disease concurrently.

Ocular toxocariasis is typically a unilateral disorder, but confirmed cases of bilateral panuveitis have been reported.

Demographics

• The overall prevalence of Toxocara infection of the eye is about 1% of the general uveitis population.
  
• Visceral larva migrans usually presents around the age of 2 years.
  
• Most cases of ocular toxocariasis occur in children 5 to 10 years of age, with a range of 2 to 30 years. By the time the child seeks eye care, systemic manifestations have usually resolved.
  
• The largest number of cases of ocular toxocariasis has been reported in the United States; however, the disease has been seen in many countries worldwide.

Significant History

• Is there known exposure to puppies, especially 2 weeks to 6 months of age? (>50% of puppies and 20% of adult dogs harbor the parasite)
  
• Is there a history of geophagia?
  
• Did the child play in a sand box?
  
• Is there a history of ingesting uncooked foods?

Ancillary Tests

The diagnosis of both visceral larva migrans and ocular toxocariasis is typically made based on the appropriate signs and symptoms, together with a history of exposure to infected pets or pica. In atypical cases, the diagnosis can be aided by an ELISA titer of undiluted serum, which has a high sensitivity and specificity (90%) for toxocara antibodies.

Occasionally, in cases of ocular toxocariasis, the serum ELISA titers may be normal but antibody titers of intraocular fluids may be elevated which permits a diagnosis. Unfortunately, ELISA analysis of intraocular fluids may only be available at a few isolated facilities.

Visceral larva migrans is often associated with a marked leucocytosis, with 30% to 80% due to eosinophils. Ocular toxocariasis is usually not associated with a peripheral eosinophilia; however, eosinophils found in the vitreous can be helpful in the diagnosis.

Ultrasonography, to detect the intraocular calcifications of a retinoblastoma, can assist in the differential diagnosis. B-scan can also be helpful when vitritis or other opacities preclude a view of the fundus.

Optical coherence tomography can image the posterior pole granulomas and show factors contributing to vision loss such as intraretinal or subretinal fluid.

The Treatment

Suggested regimens for ocular toxocariasis may include a combination of the following:

• albendazole 400 mg p.o. b.i.d. for 5 days. Use is controversial
  
• prednisone 30 to 60 mg p.o. q.d. for 5 to 10 days followed by taper to control the vitreitis (in some cases, periocular injections of steroids may be preferable to oral usage).

Anterior uveitis, if present, is typically mild and should be treated with topical steroids and cycloplegics as clinically indicated.

If subretinal larva is visualized outside the foveal area, photocoagulation or cryocoagulation may be used to destroy the organisms.

Surgery is sometimes required for complications such as tractional retinal detachments.

Note: Controlling toxocara infections in dogs and puppies is essential if there are children in the household. Complete cooking of meats, thorough rinsing of fruits and vegetables, and hand washing are important measures for preventing the human infection.

Age-Related Macular Degeneration

Nakhleh E. Abu-Yaghi, Helmut Buettner, Sophie J. Bakri

ICD-9: 362.50

     THE DISEASE

Pathophysiology

As the macula ages, many ultrastructural changes occur: the photoreceptors are reduced in density and distribution, residual bodies accumulate in the retinal pigment epithelium (RPE), basal laminar deposits form in Bruch’s membrane, and the choriocapillaris starts to involute. Age-related macular degeneration (AMD) is a distinct process that is characterized by specific non-neovascular and neovascular abnormalities.

Drusen are the hallmark of non-neovascular AMD. They are small round yellowish lesions corresponding to abnormal thickening of the inner aspect of Bruch’s membrane. Histologically, granular lipid rich materials with widely spaced collagen fibers form basal laminar deposits, whereas phospholipid vesicles and electron-dense granules form basal linear deposits within the inner aspect of Bruch’s membrane. This thickened Bruch’s inner layer, together with the RPE, can separate from the rest of Bruch’s membrane to form a pigment epithelial detachment.

Other non-neovascular abnormalities in the RPE include contiguous areas of RPE loss or attenuation, termed geographic atrophy. This is associated with loss of the overlying photoreceptors. Focal hyperpigmentation of the RPE is another non-neovascular change and is a risk factor for progression to the more advanced forms of AMD.

All non-neovascular changes increase the chance of a break occurring in Bruch’s membrane, allowing neovascular tissue from the choriocapillaris to perforate the outer aspect of Bruch’s membrane. This is neovascular or exudative AMD. Fibrovascular proliferation can occur, disrupting the normal architecture of the outer retina. A disciform scar can eventually form.

Etiology

The Patient

Clinical Symptoms

• Initially may be asymptomatic
  
• Blurred vision
  
• Metamorphopsia
  
• Central blind spot

Clinical Signs

Ancillary Tests

In addition to a detailed eye examination including biomicroscopy, a number of tests are extremely helpful in diagnosing and managing patients with AMD. The Amsler grid allows the detection and localization of changes in the central visual field caused by AMD. It also allows the patient with AMD to self-monitor the central visual field for the development of visual symptoms or their changes. FA is extremely helpful in the identification and classification of anatomic and functional abnormalities associated with AMD. Occasionally, indocyanine green angiography used as an adjunct can be helpful in visualizing the choroidal neovascular membrane (CNV) when it is obscured by blood. These angiographic techniques are particularly useful in determining the location and size of the CNV, important for the planning and performance of their treatment. Optical coherence tomography (OCT) can provide cross-sectional high-resolution images of the retina, pigment epithelium, and inner choroid in the macular area, helpful in diagnosing and monitoring the disease or its response to treatment.

The Treatment

Population-based studies have shown that individuals who have consumed a diet rich in antioxidants (green leafy vegetables, red wine) throughout their lives have a lower risk of developing and losing vision from AMD. These studies led to a large, prospective randomized trial of the effect of high-dose vitamins and minerals on the progression of AMD in patients with large drusen in the macula. The Age-Related Eye Disease Study (AREDS) supplements consists of daily doses of vitamin A (28,000 units), vitamin C (500 mg), vitamin E (400 IU), zinc (80 mg), and copper (2 mg). In the AREDS, individuals who received these vitamins and mineral supplement had a lower risk of both progression of their AMD and visual loss from AMD as compared to individuals who received a placebo. Other measures aimed at preventing development or progression of AMD include cessation of smoking, optimal control of cardiovascular disease and risk factors, and minimizing exposure to UV by wearing appropriate UV-blocking glasses. The AREDS 2 study is currently evaluating the effects of high supplemental doses of dietary xanthophylls (lutein and zeaxanthin) and omega-3 long-chain polyunsaturated fatty acids on the development and progression of AMD. In this study, beta carotene (vitamin A) has been eliminated from the original AREDS formulation, and the dose of zinc has been reduced from 80 to 25 mg.

Several ongoing clinical trials are looking for treatment options for geographic atrophy. One example is the complement inhibitors, given systemically or intravitreally the evolution to atrophic AMD.

Treatment of Exudative AMD

Photodynamic therapy (PDT), a combination of the photosensitizing drug verteporfin and infrared laser irradiation, was evaluated in many studies to treat exudative AMD. A large randomized collaborative study (Treatment of Age-Related Macular Degeneration with Photodynamic Therapy) showed that 67% of eyes with predominantly classic subfoveal neovascularization treated with verteporfin had lost fewer than 15 letters of vision after 12 months as compared to only 39% of eyes treated with placebo. The verteporfin treatment benefit was still present after 2 years. The verteporfin in photodynamic therapy trial evaluated treatment of subfoveal occult CNVs. At 2 years, 45% of treated eyes lost fewer than 15 letters compared to 32% of sham-treated eyes. These studies showed that PDT reduces the risk of further loss in vision by around 50%. In the pre–anti-VEGF (vascular endothelial growth factor) era, PDT was an appropriate treatment for subfoveal CNV, new or recurrent, in predominantly classic lesions, or occult lesions with a visual acuity of 20/50 or worse, or with a visual acuity of better than 20/50 with a lesion size less than a disc diameter.

The pharmacologic inhibition of VEGF is the mainstay of treatment in wet AMD currently. Ranibizumab (Lucentis) is a recombinantly produced, humanized antibody (Fab) fragment that binds VEGF and is FDA-approved to treat wet AMD as an intravitreal injection. Studies have shown that 95% of ranibizumab-treated individuals experienced visual improvement or stabilization compared to 62% of sham-treated patients after 12 months, with 40% of treated patients achieving improvement by 15 letters or more. Multiple re-treatments are necessary, sometimes at monthly intervals for several years, and this can be guided by both clinical and imaging parameters. Bevacizumab (Avastin) is a full-length monoclonal antibody against VEGF approved for metastatic colorectal cancer, but it is widely used off-label to treat wet AMD. A randomized, multicenter, clinical trial, the CATT trial (Comparison of ARMD Treatments Trials), is designed to compare the efficacy and safety of bevacizumab and ranibizumab.

Combination treatment is a tempting option for many reasons. The complexity of the disease calls for a treatment approach that offers synergistic modes of action to target the multiple components of AMD and to reduce the frequency of re-treatments and stabilize the visual improvement. The FOCUS study and the PROTECT trial evaluated the safety and efficacy of ranibizumab in combination with PDT versus PDT alone. At 1 year, 91% of treated subjects had stable vision compared with 68% under PDT alone. The number of PDT sessions was 2.3 in the combination subjects versus 3.4 in monotherapy. Similar results were reported from two nonrandomized studies that evaluated the combination of bevacizumab and PDT. Combining intravitreal steroids with PDT and/or anti-VEGF treatments is also an attractive option. Corticosteroids inhibit VEGF expression, vascular permeability, and inflammation, and using them in combination appears to be safe, especially in pseudophakic patients.

Low vision rehabilitation remains an important part of advanced AMD management and should be offered to all patients with bilateral advanced disease.

Stargardt’s Disease

Jerome Sherman

ICD-9: 362.75

     THE DISEASE

Stargardt’s disease or dystrophy, occasionally termed juvenile macular dystrophy, is the most common form of inherited juvenile macular degeneration. It is characterized by progressive and symmetrical atrophy of the macula that affects individuals with previously normal vision. Stargardt’s disease is often considered a form of fundus flavimaculatus, where macular atrophy predominates early in the disease progression. Perhaps, the most accurate name is “Stargardt’s Disease with Fundus Flavimaculatus” because most patients have both the macular atrophy and the characteristic flecks.

Pathophysiology

Although most eye clinicians regard Stargardt’s disease and fundus flavimaculatus as different manifestations of the same disease, for classification purposes, they are interchangeable. The term fundus flavimaculatus is applied when the characteristic subretinal flecks, which are fish-tail or pisciform in shape, are scattered throughout the fundus. When the flecks are very subtle, confined to the posterior pole or nonexistent, the macular atrophy is properly termed Stargardt dystrophy. Although some patients present initially with only the macular atrophy while others present with only the flecks, long-term follow-up of either group reveals the eventual ophthalmoscopic finding of both the macular atrophy and the characteristic flecks.

Stargardt’s disease has its onset within the first two decades of life. A patient initially presents with a decrease in visual acuity. Although visual acuity loss is often proportional to the degree of macular atrophy, it is not at all rare for a patient to present with reduced visual acuity but with a normal appearing fundus. Numerous patients with an eventual diagnosis of Stargardt’s disease have been initially misdiagnosed as malingering. Macular lesions may precede the flecks. Thus, the diagnosis of Stargardt’s disease is sometimes made before other signs of fundus flavimaculatus are evident.

Etiology

Stargardt’s disease is most typically a result of an autosomal recessive gene. As with all autorecessive disorders, a high incidence of consanguinity can be established through the appropriate questions. A very small number of families have an autosomal dominant form. All autosomal recessive forms of Stargardt’s and fundus flavimaculatus have been mapped to the short arm of chromosome 1. The autosomal dominant form of these disorders map to chromosome 13q34 and the long arm of chromosome 6. It has been found that the causal gene of Stargardt’s disease, ABCA4 (located on the short arm of chromosome 1), is a mutated photoreceptor cell-specific adenosine triphosphate–binding transporter. It is expressed in rod but not cone photoreceptors. The variations in sequencing of the ABCA4 gene appear to be responsible for the varied clinical presentations observed in patients with Stargardt’s dystrophy.

The Patient

Clinical Symptoms

Clinical Signs

The onset of Stargardt’s disease is usually in the first or second decade of an individual’s life. The most characteristic finding of Stargardt dystrophy is a progressive and symmetrical atrophy of the macula with previously normal vision. Visual acuity initially varies from 20/25 to 20/60 and progresses to 20/200. Although the progression of visual loss is variable, it is generally found to be similar with members of the same pedigree.