Ординатура / Офтальмология / Английские материалы / Clinical Ocular Pharmacology 5th edition_Bartlett, Jaanus_2008

654 CHAPTER 32 Thyroid-Related Eye Disease

In many instances, however, the patient’s primary desire is to have an improved cosmetic appearance of the eyelid retraction. Because the relationship between the clinical signs of thyrotoxicosis and the effects of increased catecholamine activity has been apparent for many decades, various attempts have been made to control or alleviate the upper lid retraction by using adrenergic blocking agents, such as guanethidine, reserpine, and thymoxamine. Because upper eyelid retraction may be mediated through sympathetic activity of Müller’s muscle, drugs with α-adrenergic blocking properties have been used topically and orally to manage this condition. However, these drugs do not affect the degree of proptosis, if present, because proptosis is associated with increased volume of the retrobulbar tissues and is not mediated through autonomic nervous system control. Topical bethanidine, an adrenergic blocking agent, has been used in 10% and 20% solutions to treat eyelid retraction. When used in a dosage of two or three drops daily, it effectively induces a pharmacologic Horner’s syndrome with associated ptosis and miosis. Three or more weeks may be required to reach a maximum ptotic effect. No serious adverse ocular or systemic side effect has been observed. Propranolol, a β-adrenergic blocking agent, has been used both orally and topically to relieve lid retraction. For acute cases of eyelid retraction, propranolol, 10 mg four times daily, may be helpful. The topical use of 1% propranolol solution has produced variable results. In addition, topical timolol has been used by some practitioners for eyelid retraction, but with variable degrees of success.

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Dapiprazole HCl (Rev-Eyes) is an α-adrenergic blocking agent introduced for the treatment of iatrogenically induced mydriasis. One of the side effects of this topical agent is ptosis. In theory, this effect could potentially be useful for early eyelid retraction of Graves’ disease. Other side effects, however, include burning on instillation and moderate to severe conjunctival injection. There has been no published study about the efficacy of dapiprazole to relieve eyelid retraction in class 1 disease.

The drug used most commonly for the relief of eyelid retraction is orally or topically administered guanethidine. Guanethidine depletes sympathetic storage sites, initially causing release of norepinephrine that may lead to mydriasis and lid retraction but that eventually produces a chemical sympathectomy resembling postganglionic Horner’s syndrome. Although guanethidine is somewhat unpredictable in the management of eyelid retraction, it seems to offer the best results with the fewest toxic effects when used in lower concentrations. Orally administered guanethidine, 15 mg/day, has been shown to lower the eyelid in some patients, but most clinicians prefer the topical route of administration. Additionally, the use of oral guanethidine may have severe systemic side effects in some patients.

When used topically in a 10% concentration, guanethidine substantially reduces lid retraction but is associated

with significant superficial punctate keratitis in approximately 50% of patients. The 5% solution is equally effective but without the attendant side effects. Unlike the effect associated with thymoxamine, the beneficial effect is usually observed in the first 72 hours after treatment is initiated (Figure 32-9). It was found that the ptosis produced by 5% topical guanethidine was approximately 1.5 mm. Systemic side effects have not been noted in most studies, but a report of two patients with severe abdominal pains and diarrhea requiring emergency hospital admission should call for caution in the use of this drug. The clinician should initiate therapy with 5% guanethidine, one drop three times daily, until maximum improvement in the eyelid position is obtained and then should reduce the frequency of administration to daily instillation if this is adequate and, if possible, further reduce the instillation to alternate days.

Several conditions may adversely affect the ability of guanethidine to lower the upper eyelid: (1) if the patient is thyrotoxic rather than euthyroid or hypothyroid; (2) if the patient is concomitantly undergoing drug therapy with adrenergic agonists, either systemically or topically; and (3) if adhesions form between the levator and the superior rectus muscles in the later stages of the disease process.

If conservative measures are insufficient to promote patient comfort or acceptance, botulinum A toxin can be injected directly into the affected levator muscle. Injection of 2.5 to 7.5 units of toxin may lower the affected

Days of treatment

Figure 32-9 The mean decrease in palpebral fissure of one eye as compared with pretreatment values in 14 patients receiving 10% guanethidine, two drops twice daily. Each point represents the mean (± SEM). Measurements were obtained by projecting the clinical photographs to eight times their original size. (Reprinted with permission from Sneddon JM, Turner P. Adrenergic blockade and the eye signs of thyrotoxicosis. Lancet 1966;2:525–527.)

eyelid by 2 to 3 mm.The effect is short term and difficult to predict.

Surgery for class 1 disease is usually not indicated because affected patients are typically asymptomatic and because the eyelid retraction may resolve after treatment of the underlying thyrotoxicosis. Surgery, however, is a reasonable and necessary alternative for patients with severe eyelid retraction not responding to more conservative measures. The two most common reasons for surgical repair are cosmesis and relief of symptoms arising from ocular exposure. Surgical extirpation of Müller’s muscle in combination with severance of the levator aponeurosis from its attachments produces successful reduction in eyelid retraction. In some patients with fibrosis of the inferior rectus muscle, recession of the tight muscle may reduce or eliminate upper eyelid retraction. Eyelid retraction procedures seem to be most effective in patients with minimum to moderate proptosis (<25 mm). In most cases surgery for eyelid retraction should not be considered until the ocular condition has been stable for at least 6 months to 1 year. If proptosis is present and is severe enough to require orbital decompression, this procedure should be performed first, because the decompression itself may reduce the eyelid retraction. The decision to lower the lids should then be postponed for several months. However, in emergencies in which corneal integrity is threatened, eyelid surgery could be contemplated together with the orbital decompression.

Class 2 Disease (Soft Tissue Involvement)

In many patients mild class 2 disease can be managed adequately with ocular lubricants. Elevating the head of the bed on 6-inch blocks during sleep can minimize eyelid and periocular swelling on awakening. Reduction of periorbital swelling may be measured by inserting a small straight-edged ruler into the upper eyelid fold and allowing periorbital tissue to rest on it. The number of millimeters the periorbital tissue covers is a quantitative measure of the swelling. The use of tinted lenses may provide relief from light sensitivity.Tinted lenses not only guard against irritation and light sensitivity but also have the advantage of masking the cosmetic problem. Occasionally, the use of orally administered diuretics may be of help, but it is open to debate whether diuretics, used in the past, provide relief. For patients with moderate to severe class 2 disease, the use of systemically administered corticosteroids may be of immense benefit (Figure 32-10).There is no doubt that the use of steroids in adequate dosages can decrease the severity of ocular complications, although these agents have minimal, if any, influence on the duration of the thyrotoxicosis. The use of systemic steroids seems to have the greatest benefit for patients with acute orbitopathy.

Locally administered steroids have been used with variable success. Although topically applied steroids are completely ineffective in alleviating the ocular signs or symptoms associated with class 2 disease, periocular

Figure 32-10 Same patient as in Figure 32-3 after systemic steroid therapy. Note the marked improvement in eyelid swelling, conjunctival and episcleral injection, and chemosis.

steroids have been used with some success.Subconjunctival or retrobulbar injections of methylprednisolone are used, and sub-Tenon’s capsule injection of aqueous triamcinolone (Kenalog), 40 mg/ml, can also be used. The precise dosage of methylprednisolone must be guided by the individual patient,but 10 to 20 mg per injection (40 mg/ml) has been effective when repeated at varying intervals. More concentrated preparations of methylprednisolone (Depo-Medrol), 80 mg/ml, permit the injection of higher doses with smaller volumes, which is particularly important in giving retrobulbar injections into an already tense orbit. Patients should be advised that transient proptosis may occur after the injection. In a recent randomized clinical trial peribulbar injections of 20 mg triamcinolone acetate (four injections at weekly intervals) were associated with a substantial improvement in diplopia and reduction in EOM (extraocular muscles) dysfunction. Periocular injections may be repeated at monthly or longer intervals, as required. One major advantage of retrobulbar injections of long-acting steroids is the minimized systemic effects when compared with the oral and intravenous routes.

High-dose oral glucocorticoids have been the mainstay in the management of Graves’ orbitopathy. In general, favorable effects have been observed on inflammatory signs and optic nerve involvement, whereas the effects on the extraocular muscle involvement and especially proptosis have not been constantly impressive. Two recent randomized controlled clinical trials addressed the question of whether intravenous glucocorticoids are more effective than oral glucocorticoids. Although both treatments proved to be effective,the proportion of favorable responses was higher in patients treated by intravenous glucocorticoids. The intravenous treatment was also better tolerated than the oral treatment. One major concern of high-dose systemic glucocorticoid treatment is the potential risk of side effects and complications.

Orbital radiotherapy has been used to treat thyroid orbitopathy for the past 60 years. Its therapeutic use is still

656 CHAPTER 32 Thyroid-Related Eye Disease

studied and debated to this day. Studies using sham versus orbital radiotherapy concluded it had some beneficial effect on early and mild orbitopathy. Several other studies attempted in the United States failed to show any beneficial effect from the radiotherapy. It is a therapy option that should be agreed on by both doctor and patient after careful consideration.

Class 3 Disease (Proptosis)

Because proptosis is not an isolated finding and is more commonly a variable finding in Graves’ ophthalmopathy, it is not a useful indication of the degree of orbital infiltration or of the response to treatment. Moreover, longstanding proptosis tends to be permanent, presumably because of the permanent changes in the tissues of the orbit, and is thus not often amenable to medical therapy.

As stated, Graves’ ophthalmopathy worsens in many patients despite antithyroid therapy, especially in therapies that cause rapid alteration in thyroid tissue and function. More recent studies suggested that, as compared with other forms of antithyroid therapy, 131I is more likely to be followed by the development or exacerbation of Graves’ ophthalmopathy. This may reflect only the increase in thyrotropin-receptor antibody and other thyroid antibodies in serum after destruction of the thyroid gland by RAI. Consideration should be given to initiating oral steroid therapy before 131I therapy.

Proptosis, as an isolated finding, rarely requires treatment unless there is secondary exposure keratopathy or unless it represents a significant cosmetic problem. Affected patients may benefit from a trial of systemic corticosteroids. A significant decrease in the severity of proptosis may be observed in some patients. In general, if regression of the proptosis occurs after the institution of steroid therapy, it will begin soon after the onset of therapy and reach a maximum in 2 or 3 months. If no response to steroid therapy is seen after 3 to 4 weeks, the therapy should be discontinued.As mentioned previously, response to corticosteroid therapy for proptosis is variable at best.

Class 4 Disease (Extraocular Muscle Involvement)

Some patients, perhaps up to 20%, may experience return of normal eye movements after medical control of the thyrotoxicosis. For patients who do not experience improvement, the only pharmacologic interventions shown to be effective for the specific changes associated with class 4 disease are systemic prednisone and local injections of botulinum toxin, though both modalities are rarely used, for motility signs alone, in modern therapy.

In the early stages of class 4 involvement, treatment with small doses of prednisone may be initiated when control of the hyperthyroidism or adequate therapy of hypothyroidism has not arrested the ocular activity. Improvement in motility usually occurs within 4 to 12 weeks. Many patients experience enough subsequent improvement in ocular motility so that severe class

4 disease may be considered a relative but not absolute indication for steroid therapy. However, conservative therapy is prudent in many cases and may include vision therapy to lessen the tendency for muscle fibrosis; the use of Fresnel prisms, which have a definite advantage in the management of unstable motility disorders; or simple monocular patching.

Many patients should be considered surgical candidates after the failure of steroid therapy or other more conservative therapeutic measures. Marked improvement can often be obtained in elevation of the globe and amelioration of the diplopia, after appropriate recession of the fibrotic rectus muscle. The recession of other extraocular muscles to correct existing heterotropias and associated diplopia should also be considered. Adjustable suture surgery has been used in many centers to eliminate diplopia in the primary and reading positions and has been found to provide long-term symptomatic relief in most patients. When the inferior rectus is recessed, reattachment of the lower lid retractors is critical to avoid lower lid lag, aggravating exposure. In general, surgery should be postponed for at least 6 to 12 months after stabilization of the metabolic and ocular conditions, because early surgical manipulation may acutely exacerbate the original disease process. Significant complications from eye muscle surgery are rare but include an increase of the proptosis after release of the fibrotic ocular muscles. For this reason, if the proptosis is more than 24 mm, consideration should be given to orbital decompression before muscle surgery, even if there is no significant threat to vision.

Class 5 Disease (Corneal Involvement)

Patients with class 5 disease are at risk of serious ocular complications and loss of vision. This stage of disease occurs in patients with enough proptosis to prevent adequate eyelid closure, resulting in chronic corneal exposure. Complicating factors may include extraocular muscle involvement sufficient enough to obliterate Bell’s phenomenon. In the milder forms of exposure, the administration of bland ocular lubricants at bedtime or continuously during the day may be of significant benefit in alleviating associated symptoms and preventing or delaying more serious ocular involvement. The topical application of broad-spectrum antibiotics (e.g., trimethoprim sulfate–polymyxin B) may be indicated for the prophylaxis of infection. Taping the eyelids shut at bedtime or using a plastic-wrap shield may also prove beneficial. When frank corneal ulceration is imminent, frequent use of topical broad-spectrum antibiotics (e.g., moxifloxacin) and systemic steroid therapy can prove useful. The use of systemic or intravenous steroids sometimes obviates the need for surgery (orbital decompression) but generally involves long-term therapy with the possibility of adverse effects. Steroids are also useful for patients who cannot undergo orbital decompression or lateral tarsorrhaphy because of a contraindication to general anesthesia.

Orbital decompression should be considered for patients with severe class 5 disease for whom steroids, orbital radiation,and other medical therapies have proven to be ineffective or contraindicated. This might include patients whose compliance may be poor or for whom follow-up may be difficult.

Class 6 Disease (Optic Nerve Involvement)

The incidence of optic neuropathy in thyroid eye disease is 2% to 9%, but it is a particularly treacherous complication, because patients often do not have marked proptosis and do not have evidence of optic nerve head changes on fundus examination. Although as many as 70% of patients with optic neuropathy spontaneously experience improvement without treatment, the risk to vision is significant, and loss of vision may become permanent if the optic neuropathy is not quickly recognized and aggressively treated. The most common presentation is a patient with a complaint of visual acuity loss or a visual field defect (Figure 32-11). Patients may also manifest color defects, afferent pupillary defects, and abnormalities on visual evoked potential testing. High-resolution CT or MRI often confirms suspect cases of optic disc edema. Ideally, therapy should begin with correction of the thyroid imbalance. Replacement thyroid hormone is mandatory for hypothyroid states. Some patients with optic neuropathy have been managed by adjustment of the thyroid state, but these patients must be monitored closely.

A gratifying response to high-dose steroid therapy may be observed in many patients with optic neuropathy (see Figure 32-11). About two-thirds of patients have reduction in their symptoms and swelling in about 1 week. One study reported a 48% success rate defined as two Snellen lines of improvement in visual acuity within 2 months of steroid treatment.

Guidelines for the management of patients with optic neuropathy are as follows:

1.Patients with minimum optic nerve dysfunction (visual acuity of 20/30 [6/9] or better) may be managed by observation alone. However, the tendency for rapid progression demands serial examinations of visual acuity, visual fields, and pupillary testing.

2.Patients with progressive vision loss (with or without disc swelling) or with disc swelling and no visual defect should be treated. Oral or intravenous steroids in large doses remain the primary therapeutic modality, but if a response has not occurred within 3 or 4 weeks, continued high doses are not likely to succeed.

3.Prolonged steroid maintenance without improvement in visual function is not justified.

Systemic Management of Ophthalmopathy

As mentioned, the hyperthyroid state must be controlled before using other therapeutic measures,including steroids and immune-modifying agents. Systemic treatment with

steroids or immunomodulators, either alone or in combination with other treatments, is based on the fact that Graves’ ophthalmopathy is the consequence of an autoimmune process. These treatments attempt to relieve inflammatory or congestive signs by shrinking tissues within the orbit, resulting in decreased intraorbital pressure.

Steroids

Systemic steroids often effectively control the optic neuropathy and other inflammatory changes of the ophthalmopathy. However, systemic steroids must be used in high dosages at the expense of their known complications and side effects, including osteoporosis, hyperglycemia, systemic hypertension, infection, gastric ulceration, cataract, cushingoid features, and psychosis. However, rapid progression of proptosis, ophthalmoplegia, and optic nerve involvement warrant such treatment. Developments of visual field defects and decreased visual acuity are absolute indications for the use of highdose steroids. Assuming there are no life-threatening contraindications to the use of steroids, high-dose steroids as monotherapy are of use in ameliorating many of the inflammatory features of the orbitopathy. Patients who benefit do so very early in the course of treatment. Subjective improvement might occur within the first 24 hours, and extraocular muscle function and visual acuity might improve in a few days or weeks. Treatment should be initiated with large doses of prednisone (80 to 100 mg/day).When improvement is apparent, the dosage should be reduced gradually. Decreasing the dosage by 5 to 10 mg a week is a safe guideline. Whenever exacerbation occurs, the dosage should be increased to the initial treatment level. Subsequently, the steroid should be tapered more gradually.

In the last 10 years or so steroids have been used intravenously by the acute administration of high doses of methylprednisone acetate (0.5 to 1.0 g) at different intervals. The cumulative dose of steroid ranges from 1 to 21 g in different studies. In general, favorable effects have been observed on inflammatory signs and optic nerve involvement, whereas the effects on extraocular muscle involvement, and especially proptosis, have not been consistent or impressive.

In general, if optic neuropathy is responsive to steroids, exacerbations occur if the drug is withdrawn within 2 to 4 weeks. Therefore steroids must be administered until the disease process undergoes spontaneous remission. Although this increases the potential risk of serious steroid-related complications, the risk is justified in many instances. Because of the risks inherent in systemic steroid therapy, the practitioner should educate the patient regarding the potential side effects of steroids and the need for regular and long-term medical supervision.

Combining steroids with cyclosporine or orbital irradiation appears to enhance the efficacy of individual therapy. Use of steroids has also been recommended to prevent

progression of Graves’ ophthalmopathy after RAI treatment of hyperthyroidism.

Plasmapheresis

Plasmapheresis is primarily used in patients with muscular dystrophy and lately with parkinsonism. However, the use of plasmapheresis in thyroid eye disease has mirrored problems observed in assessing responses in other autoimmune disease. The concept of an immune complex involvement in the pathophysiology of thyroid eye disease is unproven. A study reported 11 patients who received multiple plasmapheresis sessions with systemic prednisone and azathioprine. It noted that this form of

therapy did not affect exposure keratopathy or extraocular muscle dysfunction but appeared to diminish soft tissue involvement. In summary, plasmapheresis has provided conflicting results because both favorable effects and treatment failures have been reported. There are no randomized or controlled studies on the sole effects of plasmapheresis. This treatment modality should be regarded as a “desperate” treatment for severe orbitopathy when all other therapies have failed.

Novel Treatments for Graves’ Orbitopathy

Somatostatin receptors have been demonstrated in orbital fibroblasts and orbital lymphocytes. The use of

somatostatin analogues was first reported in an uncontrolled study of six patients treated with octreotide (0.1 mg three times a day for 3 months) who showed improvement in extraocular muscle function and soft tissue involvement. The mechanism of action of somatostatin analogues is not fully understood. The interaction of the drug with the somatostatin receptors located on the surface of the different cell types in the orbit might inhibit local release of cytokines and insulin growth factor, which appear to be relevant in triggering or maintaining ongoing inflammatory reactions in the orbital tissue of patients with orbitopathy. By 2003 less than 100 Graves’ orbitopathy patients had been treated with somatostatin analogues. Recently, two well-designed, randomized, double-blind, placebo-controlled studies

provided new insights into this potential treatment for Graves’ orbitopathy. Unfortunately, these trials cast serious doubts on the usefulness and effectiveness of somatostatin analogues in the management of Graves’ orbitopathy. However, a novel somatostatin analogue (SOM230) was developed with a higher affinity than the two (octreotide and lanreotide) somatostatin analogues used in the above-mentioned studies. Future clinical trials are required to ascertain the potential usefulness, if any, of this new somatostatin analogue.

Some evidence from in vitro studies suggests that oxidative stress in the orbit of Graves’ patients may play a role of perpetuating the inflammatory reactions in the orbital tissues.The clinical effects of nicotinamide and allopurinol were evaluated in a prospective placebo-controlled

660 CHAPTER 32 Thyroid-Related Eye Disease

nonrandomized study of 22 patients affected with mild to moderate Graves’ orbitopathy. These drugs, given orally for 3 months, showed improvement of the orbitopathy in 9 of 11 treated patients (82%) compared with 3 of 11 placebo-treated patients (27%). Improvements were mainly related to the soft tissue complications of the orbitopathy.

The use of cytokine antagonists (monoclonal antibodies to cytokines) used in the management of rheumatoid arthritis and Crohn’s disease has some beneficial effect on Graves’ orbitopathy. A recent study of 10 patients with mild to moderately severe Graves’ orbitopathy showed that the administration of etanercept, an antitumor necrosis factor drug (25 mg a week for 3 months) was associated with a significant improvement of the clinical activity score and ophthalmopathy index in approximately 60% of patients.

Additionally, a recent report showed that the use of the peroxisome proliferators activated receptor agonist (thiazolidinedione) drug, pioglitazone, in a man with type 2 diabetes mellitus and stable Graves’ orbitopathy was associated with activation and progression of the eye disease. This report suggests that thiazolidinediones may be contraindicated in Graves’ orbitopathy patients. It also opens up a potential treatment modality with antagonists to the drug class used in the management of the orbitopathy.

Finally, the orbitopathy from Graves’ disease seems to be related to autoimmune reactions directed against antigens shared by the thyroid and orbit. These antigens and the mechanisms of the disease activation are still unidentified. Lacking this knowledge makes it difficult to design immunosuppressive and immunologic intervention in the near future.

Other Forms of Management

Orbital Irradiation

Attempts at orbital irradiation were begun more than 60 years ago but involved relatively low-dose, low-energy, or poorly collimated beams. The results were generally unsatisfactory. In the last 5 years several studies addressed the issue of effectiveness and safety of orbital radiotherapy for Graves’ orbitopathy. The results have been somewhat favorable, and this approach seems to offer a reasonable alternative or additive to steroids. The irradiation has several effects on the orbital tissues, which include the biochemical effect of correcting acidosis produced by the inflammatory response and suppressing lymphocytes. The anti-inflammatory effect of irradiation is from the suppression of fibroblast production. Existing hyperthyroidism should be corrected, if possible, before irradiation. Supervoltage radiotherapy combined with corticosteroids is more effective than radiotherapy alone, blurring the true therapeutic effect of each therapy. When systemic steroids are administered simultaneously, the dose should be kept constant during the period of irradiation and for several weeks thereafter.

In general, orbital irradiation produces the most impressive results in patients with active and mild ophthalmopathy, rather than in patients with a more indolent disease course. The decision to use orbital radiation is on a case-by-case basis. Patients with diabetic retinopathy, patients presently on chemotherapy, and patients who have had prior head irradiation should not be considered for orbital irradiation.

Orbital Decompression

Orbital decompression is used to salvage the eye and vision when extreme proptosis with corneal exposure or optic nerve compression does not respond to medical therapy. Presently, approximately one-half of the orbital decompression procedures are performed for the reduction of proptosis, as a cosmetic procedure. As many as 40% of these procedures are now performed for cosmesis. Orbital decompression for Graves’ ophthalmopathy was first reported in 1911. Since then, several surgical approaches for orbital decompression have been described (Figure 32-12). In 1931 the concept of removal of the roof of the orbit by a neurosurgical transfrontal approach, the Naffziger approach, was introduced. Another approach, the Kronlein procedure, involves removing the lateral wall of the orbit with decompression into the temporal fossa. Both procedures have the disadvantage of decompressing the orbit into an area of high tissue pressure. In addition, the Naffziger approach introduces the morbidity of an intracranial operation, and the Kronlein method is a lengthy procedure involving considerable bony resection. The Walsh-Ogura (transantral resection of the medial and inferior walls of the orbit) became the mainstay for orbital decompression after its report in 1957, but chronic new diplopia was a frequent sequela.

The decompressive procedure used most commonly for Graves’ orbitopathy today is the medial inferior decompression through either a transantral or translid approach. In 1992 using a transorbital three-wall decompression

Figure 32-12 Approaches for orbital decompression. (Modified from Char DH. Thyroid eye disease,ed. 2. New York: Churchill Livingstone, 1990.)

through a modified blepharoplasty incision was reported. This technique allowed a single incision with wide exposure, a low incidence of permanent strabismus, lateral orbital rim and canthal tendon preservation, and a large reduction in proptosis. Many ophthalmic surgeons still use modifications of the Walsh-Ogura procedure, but regardless of the technique used, surgical experience is without question a major factor in success rate.

Recent advances include the use of a fornical incision, which is considered a technical advance in decompression surgery because it allows good views of the medial and lateral walls of the orbit. Additionally, a transcaruncular approach to the medial wall allows easy removal of the ethmoid bones.

Because of the inherent surgical risks involved, orbital decompression should be considered only after more conservative therapeutic measures have been attempted. Orbital decompression surgery does not affect the course of the inflammatory or fibrotic components of thyroid ophthalmopathy. Therefore orbital decompression should not be considered until the thyroid state is stable.

Orbital decompression is useful in nearly all patients with compressive optic neuropathy.The relief of pressure

Table 32-4

Medical and Surgical Management of Graves’

Ophthalmopathy

Adapted and modified from Garrity JA. Graves’ ophthalmopathy: an ophthalmologist’s perspective. Thyroid Today 1992;15:1–9; and Bahn RS, Garrity JA, Gorman CA. Diagnosis and management of Graves’ ophthalmopathy. J Clin Endocrinol Metab 1990; 71:559–563.

at the orbital apex is key to surgical management. Additionally, patients with stable orbitopathy and significant exophthalmos who are willing to accept the risks of the procedure are good surgical candidates. The degree of recession of proptosis can range from 2 to 10 mm.

Postoperative diplopia is a complication of the type of surgical technique or approach used by the surgeon. As many as 70% of patients have required some form of extraocular muscle surgery after an Ogura-type decompression. Patients who require orbital decompression surgery should delay extraocular muscle surgery, because a number of patients have increased diplopia after decompression procedures. Other complications of orbital decompression include sinusitis, orbital cellulitis, late enophthalmos, globe ptosis, meningitis, epiphora, recurrent optic nerve compression, and blindness.

Graves’ ophthalmopathy severe enough to warrant high-dose steroids, orbital radiotherapy, or orbital decompression is estimated to occur in not more than 20% of patients with Graves’ disease. In most cases the disorder can be managed adequately with more conservative therapeutic measures. In most patients minor interventions that are required mainly include treatment of exposure keratopathy. Table 32-4 summarizes the current therapeutic approaches to the patient with Graves’ ophthalmopathy.

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Strabismus, defined as misalignment of the lines of sight, is a common condition affecting both children and adults with an estimated prevalence of 4% to 5%. Amblyopia, defined as a disorder in which development of the visual pathway is altered by uncorrected refractive error, strabismus, or form deprivation, is the most common cause of visual morbidity in childhood and has an estimated prevalence of 2% to 4%. The high association between the two often necessitates concurrent management of both conditions. Depending on the specific characteristics, this may involve a combination of spectacles, surgery, vision therapy, occlusion, and/or pharmacologic intervention. The pharmacologic agents used in the management of strabismus and/or amblyopia can broadly be divided into three major categories: autonomic agents, direct-acting muscle agents, and centrally acting agents (Box 33-1). Although several drugs are included in these broad categories and have been the focus of investigation, those agents currently considered to be clinically useful are a limited few and are emphasized in this chapter.

ANTICHOLINERGICS (CYCLOPLEGIC AGENTS)

The most frequent and perhaps most important use of cycloplegic agents in the treatment of strabismus and amblyopia (especially accommodative esotropia and refractive amblyopia) is to determine the appropriate spectacle prescription through a cycloplegic refraction. This refraction is an essential first step before considering other aspects of care. For accommodative esotropia, maximum cycloplegia is necessary to ascertain whether refractive correction alone or additional surgical or pharmacologic intervention is required. In cases where anisometropic amblyopia is suspected, the use of cycloplegic agents helps ensure that an accurate prescription is determined that reveals the full amount of anisometropia and hyperopia. It is important that the spectacle prescription reflects the full amount of anisometropia to ensure that the amblyopic eye receives the clearest retinal image possible under binocular

viewing conditions. It has been suggested that in some cases amblyopia may improve or completely resolve with the use of optical correction alone.

Several cycloplegic agents can be used to determine a cycloplegic refraction, but all differ in duration of action and cycloplegic effect. Although tropicamide has been demonstrated to be an effective cycloplegic in myopes and low hyperopes without amblyopia and strabismus, its effectiveness has not yet been evaluated in a large group of strabismic or anisometropic hyperopes. For this reason it is not recommended for use in this population.

The two most commonly used drugs to determine a cycloplegic refraction in amblyopic and strabismic patients are cyclopentolate and atropine. Two drops of 1% cyclopentolate ophthalmic solution is routinely used in clinical practice due to its relative strong cycloplegic effect, short onset, and relatively short duration.Atropine has the strongest cycloplegic effect, but the long duration of action and long onset necessitate instillation several days before the appointment.

By paralyzing accommodation, cycloplegics may also reduce accommodative convergence.This may result in a decrease in the angle of deviation in a child with accommodative esotropia. Despite the decrease in the strabismus, the resulting blur and risk of inducing amblyopia virtually necessitate the concomitant use of optical correction. The blur at distance, and especially at near, resulting from the primary effect of anticholinergic agents may still prove important and useful as an “encouragement” for spectacle compliance. Initially, children may have difficulty in relaxing their level of habitual accommodation, leading to rejection of moderate to highpowered hyperopic spectacles.To facilitate acceptance, a cycloplegic agent may be used for a period of several weeks in both eyes. The only way to obtain clear vision under cycloplegia in moderate to high hyperopic patients is through the use of their spectacles. After acceptance of the prescription, the cycloplegic agent is discontinued. Affected children usually continue to wear the spectacles, even after the effects of the cycloplegic agent have completely worn off.